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Trabectedin

trabectedin is a tetrahydroisoquinoline alkaloid isolated from the marine tunicate Ecteinascidia turbinate with potential antineoplastic activity. Binding to the minor groove of DNA, trabectedin inteferes with the transcription-coupled nucleotide excision repair machinery to induce lethal DNA strand breaks.and blocks the cell cycle in the G2 phase. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus).

According news published on July 7, 2010 — Trabectedin (Yondelis) has been approved in Europe, Canada, and other regions of the world for use in platinum-sensitive recurrent ovarian cancer, but it is not available in the United States. On the basis of the data from a pivotal phase 3 trial that resulted in its approval elsewhere, the drug was rejected last year by a US Food and Drug Administration (FDA) advisory committee (the vote was 14 to 1 against approval, as reported by Medscape Oncology at the time).

According to http://en.wikipedia.org/wiki/Trabectedin.: Trabectedin (also known as ecteinascidin 743 or ET-743) is an anti-tumor drug. It is sold by Zeltia and Johnson and Johnson under the brand name Yondelis. It is approved for use in Europe, Russia and South Korea for the treatment of advanced soft tissue sarcoma. It is also undergoing clinical trials for the treatment of breast, prostate, and paediatric sarcomas. The European Commission and the U.S. Food and Drug Administration (FDA) have granted orphan drug status to trabectedin for soft tissue sarcomas and ovarian cancer. In 2008 it was announced the submission of a registration dossier to the European Medicines Agency (EMEA) and the FDA for Yondelis when administered in combination with pegylated liposomal doxorubicin (Doxil, Caelyx) for the treatment of women with relapsed ovarian cancer.

Discovery and development

(the following information was directly from http://en.wikipedia.org/wiki/Trabectedin).

During the 1950s and 1960s, the National Cancer Institute carried out a wide ranging program of screening plant and marine organism material. As part of that program extract from the sea squirt Ecteinascidia turbinata was found to have anticancer activity in 1969. Separation and characterisation of the active molecules had to wait many years for the development of sufficiently sensitive techniques, and the structure of one of them, Ecteinascidin 743, was determined by KL Rinehart at the University of Illinois in 1984. Rinehart had collected his sea squirts by scuba diving in the reefs of the West Indies.  The Spanish company PharmaMar licensed the compound from the University of Illinois before 1994[citation needed] and attempted to farm the sea squirt with limited success. Yields from the sea squirt are extremely low - it takes 1 tonne of animals to isolate 1 gram of trabectidin - and about 5 grams were believed to be needed for a clinical trial so Rinehart asked the Harvard chemist E. J. Corey to search for a synthetic method of preparation. His group developed such a method and published it in 1996. This was later followed by a simpler and more tractable method which was patented by Harvard and subsequently licensed to PharmaMar. The current supply is based on a semisynthetic process developed by PharmaMar starting from Safracin B, an antibiotic obtained by fermentation of the bacterium Pseudomonas fluorescens. PharmaMar have entered into an agreement with Johnson and Johnson to market the compound outside Europe.  Trabectidin was first dosed in humans in 1996.  In 2007, the EMEA gave authorisation for the marketing of trabectidin, under the trade name Yondelis, for the treatment of patients with advanced soft tissue sarcoma, after failure of anthracyclines and ifosfamide, or who are unsuited to receive these agents. The agency's evaluating committee, the CHMP observed that trabectidin had not been evaluated in an adequately designed and analysed randomised trial against current best care, and that the clinical efficacy data was mainly based on patients with liposarcoma and leiomyosarcoma. However the pivotal study did show a significant difference between two different trabectidin treatment regimens, and due to the rarity of the disease the CHMP considered that marketing authorisation could be granted under exceptional circumstances. As part of the approval PharmaMar agreed to conduct a further trial to identify whether any specific chromosomal translocations could be used to predict responsiveness to trabectidin. Trabectidin is also approved in South Korea and Russia.

Current developer:  PharmaMar, Zeltia and Johnson and Johnson.

 1: D'Incalci M, Galmarini CM. A Review of Trabectedin (ET-743): A Unique Mechanism of Action. Mol Cancer Ther. 2010 Jul 20. [Epub ahead of print] PubMed PMID: 20647340.

2: Kaye SB, Colombo N, Monk BJ, Tjulandin S, Kong B, Roy M, Chan S, Filipczyk-Cisarz E, Hagberg H, Vergote I, Lebedinsky C, Parekh T, Santabárbara P, Park YC, Nieto A, Poveda A. Trabectedin plus pegylated liposomal doxorubicin in relapsed ovarian cancer delays third-line chemotherapy and prolongs the platinum-free interval. Ann Oncol. 2010 Jul 19. [Epub ahead of print] PubMed PMID: 20643863.

3: Poveda A, Vergote I, Tjulandin S, Kong B, Roy M, Chan S, Filipczyk-Cisarz E, Hagberg H, Kaye SB, Colombo N, Lebedinsky C, Parekh T, Gómez J, Park YC, Alfaro V, Monk BJ. Trabectedin plus pegylated liposomal doxorubicin in relapsed ovarian cancer: outcomes in the partially platinum-sensitive (platinum-free interval 6-12 months) subpopulation of OVA-301 phase III randomized trial. Ann Oncol. 2010 Jul 19. [Epub ahead of print] PubMed PMID: 20643862.

4: Monneret C. [Current impact of natural products in the discovery of anticancer drugs]. Ann Pharm Fr. 2010 Jul;68(4):218-32. Epub 2010 Jun 19. French. PubMed PMID: 20637355.

5: Grimer R, Judson I, Peake D, Seddon B. Guidelines for the management of soft tissue sarcomas. Sarcoma. 2010;2010:506182. Epub 2010 May 31. PubMed PMID: 20634933; PubMed Central PMCID: PMC2903951.

6: Soini EJ, García San Andrés B, Joensuu T. Trabectedin in the treatment of metastatic soft tissue sarcoma: cost-effectiveness, cost-utility and value of information. Ann Oncol. 2010 Jul 13. [Epub ahead of print] PubMed PMID: 20627875.

7: Martinez-Trufero J, Alfaro J, Felipo F, Alvarez M, Madani J, Cebollero A. Response to trabectedin treatment in a highly pretreated patient with an advanced meningeal hemangiopericytoma. Anticancer Drugs. 2010 Jul 8. [Epub ahead of print] PubMed PMID: 20622667.

8: Del Campo JM, Muñoz-Couselo E, Diaz de Corcuera I, Oaknin A. Trabectedin combined with liposomal doxorubicin in women with relapsed ovarian cancer. Expert Rev Anticancer Ther. 2010 Jun;10(6):795-805. PubMed PMID: 20553205.

9: Simpson EL, Rafia R, Stevenson MD, Papaioannou D. Trabectedin for the treatment of advanced metastatic Soft Tissue Sarcoma. Health Technol Assess. 2010 May;14 Suppl 1:63-7. PubMed PMID: 20507805.

10: Negri T, Virdis E, Brich S, Bozzi F, Tamborini E, Tarantino E, Jocollè G, Cassinelli G, Grosso F, Sanfilippo R, Casalini P, Greco A, Pierotti MA, Pilotti S. Functional mapping of receptor tyrosine kinases in myxoid liposarcoma. Clin Cancer Res. 2010 Jul 15;16(14):3581-93. Epub 2010 Jun 3. PubMed PMID: 20522586.

11: Monk BJ, Herzog TJ, Kaye SB, Krasner CN, Vermorken JB, Muggia FM, Pujade-Lauraine E, Lisyanskaya AS, Makhson AN, Rolski J, Gorbounova VA, Ghatage P, Bidzinski M, Shen K, Ngan HY, Vergote IB, Nam JH, Park YC, Lebedinsky CA, Poveda AM. Trabectedin plus pegylated liposomal Doxorubicin in recurrent ovarian cancer. J Clin Oncol. 2010 Jul 1;28(19):3107-14. Epub 2010 Jun 1. PubMed PMID: 20516432.

12: Vincenzi B, Napolitano A, Frezza AM, Schiavon G, Santini D, Tonini G. Wide-spectrum characterization of trabectedin: biology, clinical activity and future perspectives. Pharmacogenomics. 2010 Jun;11(6):865-78. PubMed PMID: 20504257.

13: Casali PG, Sanfilippo R, D'Incalci M. Trabectedin therapy for sarcomas. Curr Opin Oncol. 2010 Jul;22(4):342-6. PubMed PMID: 20489618.

14: Italiano A, Toulmonde M, Bui-Nguyen B. [Chemotherapy options for patients with advanced soft-tissue sarcoma beyond anthracyclines]. Bull Cancer. 2010 Jun 1;97(6):679-86. Review. French. PubMed PMID: 20483708.

15: Zhang CH, Xu GL, Jia WD, Ge YS, Wang W. Can hepatocellular carcinoma be treated by Yondelis through targeting both tumor cells and tumor-associated macrophages? Hepatogastroenterology. 2010 Jan-Feb;57(97):114-6. Review. PubMed PMID: 20422884.

16: Chu Q, Mita A, Forouzesh B, Tolcher AW, Schwartz G, Nieto A, Soto-Matos A, Alfaro V, Lebedinsky C, Rowinsky EK. Phase I and pharmacokinetic study of sequential paclitaxel and trabectedin every 2 weeks in patients with advanced solid tumors. Clin Cancer Res. 2010 May 1;16(9):2656-65. Epub 2010 Apr 20. PubMed PMID: 20406837.

17: Ebada SS, Lin W, Proksch P. Bioactive sesterterpenes and triterpenes from marine sponges: occurrence and pharmacological significance. Mar Drugs. 2010 Feb 23;8(2):313-46. Review. PubMed PMID: 20390108; PubMed Central PMCID: PMC2852841.

18: Tomillero A, Moral MA. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2010 Jan-Feb;32(1):47-86. PubMed PMID: 20383346.

19: Hingorani P, Kolb EA. Past, present and future of therapies in pediatric sarcomas. Future Oncol. 2010 Apr;6(4):605-18. PubMed PMID: 20373872.

20: Germano G, Frapolli R, Simone M, Tavecchio M, Erba E, Pesce S, Pasqualini F, Grosso F, Sanfilippo R, Casali PG, Gronchi A, Virdis E, Tarantino E, Pilotti S, Greco A, Nebuloni M, Galmarini CM, Tercero JC, Mantovani A, D'Incalci M, Allavena P. Antitumor and anti-inflammatory effects of trabectedin on human myxoid liposarcoma cells. Cancer Res. 2010 Mar 15;70(6):2235-44. Epub 2010 Mar 9. PubMed PMID: 20215499.

21: Wesolowski R, Budd GT. Use of chemotherapy for patients with bone and soft-tissue sarcomas. Cleve Clin J Med. 2010 Mar;77 Suppl 1:S23-6. Review. PubMed PMID: 20179184.

22: Carter NJ, Keam SJ. Trabectedin: a review of its use in soft tissue sarcoma and ovarian cancer. Drugs. 2010 Feb 12;70(3):355-76. doi: 10.2165/11202860-000000000-00000. Review. PubMed PMID: 20166769.

23: Krikelis D, Judson I. Role of chemotherapy in the management of soft tissue sarcomas. Expert Rev Anticancer Ther. 2010 Feb;10(2):249-60. Review. PubMed PMID: 20132000.

24: Monk BJ, Coleman RL. Changing the paradigm in the treatment of platinum-sensitive recurrent ovarian cancer: from platinum doublets to nonplatinum doublets and adding antiangiogenesis compounds. Int J Gynecol Cancer. 2009 Dec;19 Suppl 2:S63-7. Review. PubMed PMID: 19955917.

25: Pick AM, Nystrom KK. Fatal hepatic and renal toxicity as a complication of trabectedin therapy for radiation-induced sarcoma. J Oncol Pharm Pract. 2009 Dec 16. [Epub ahead of print] PubMed PMID: 20015930.

26: van Waterschoot RA, Eman RM, Wagenaar E, van der Kruijssen CM, Rosing H, Beijnen JH, Schinkel AH. ABCC2, ABCC3, and ABCB1, but not CYP3A, Protect against Trabectedin-Mediated Hepatotoxicity. Clin Cancer Res. 2009 Dec 15;15(24):7616-7623. Epub . PubMed PMID: 19996204.

27: Zagouri F, Linardou H, Dimopoulos AM, Papadimitriou CA. Management of advanced stage uterine sarcomas: a bone of contention. Eur J Gynaecol Oncol. 2009;30(5):483-92. Review. PubMed PMID: 19899397.

28: Fayette J, Boyle H, Chabaud S, Favier B, Engel C, Cassier P, Thiesse P, Méeus P, Sunyach MP, Vaz G, Ray-Coquard I, Ranchère D, Decouvelaere AV, Alberti L, Pérol D, Blay JY. Efficacy of trabectedin for advanced sarcomas in clinical trials versus compassionate use programs: analysis of 92 patients treated in a single institution. Anticancer Drugs. 2010 Jan;21(1):113-9. PubMed PMID: 19887935.

29: Kasper B, Schmitt T, Wuchter P, Dimitrakopoulou-Strauss A, Ho AD, Egerer G. The use of positron emission tomography in soft tissue sarcoma patients under therapy with trabectedin. Mar Drugs. 2009 Jul 17;7(3):331-40. PubMed PMID: 19841717; PubMed Central PMCID: PMC2763103.

30: Theman TA, Hartzell TL, Sinha I, Polson K, Morgan J, Demetri GD, Orgill DP, George S. Recognition of a new chemotherapeutic vesicant: trabectedin (ecteinascidin-743) extravasation with skin and soft tissue damage. J Clin Oncol. 2009 Nov 20;27(33):e198-200. Epub 2009 Oct 5. Review. PubMed PMID: 19805684.

31: Jain A, Sajeevan KV, Babu KG, Lakshmaiah KC. Chemotherapy in adult soft tissue sarcoma. Indian J Cancer. 2009 Oct-Dec;46(4):274-87. Review. PubMed PMID: 19749457.

32: Ganjoo KN, Patel SR. Trabectedin: an anticancer drug from the sea. Expert Opin Pharmacother. 2009 Nov;10(16):2735-43. Review. PubMed PMID: 19743937.

33: Trabectedin: new drug. Soft-tissue sarcomas: too many adverse effects. Prescrire Int. 2009 Aug;18(102):161. PubMed PMID: 19743575.

34: Duan Z, Choy E, Harmon D, Yang C, Ryu K, Schwab J, Mankin H, Hornicek FJ. ZNF93 increases resistance to ET-743 (Trabectedin; Yondelis) and PM00104 (Zalypsis) in human cancer cell lines. PLoS One. 2009 Sep 9;4(9):e6967. PubMed PMID: 19742314; PubMed Central PMCID: PMC2734182.

35: Dubois EA, Cohen AF. Trabectedin. Br J Clin Pharmacol. 2009 Sep;68(3):320-1. PubMed PMID: 19740389; PubMed Central PMCID: PMC2766471.

36: Dufresne A, Blay JY, Cassier P, Vanel D, Bui B, Le Cesne A. [Recommendations for diagnostic and therapeutic management of soft tissue sarcoma]. Bull Cancer. 2009 Sep;96(9):909-15. French. PubMed PMID: 19696009.

37: Chuk MK, Balis FM, Fox E. Trabectedin. Oncologist. 2009 Aug;14(8):794-9. Epub 2009 Aug 14. Review. Erratum in: Oncologist. 2009 Sep;14(9):949. PubMed PMID: 19684073.

38: Demetri GD, Chawla SP, von Mehren M, Ritch P, Baker LH, Blay JY, Hande KR, Keohan ML, Samuels BL, Schuetze S, Lebedinsky C, Elsayed YA, Izquierdo MA, Gómez J, Park YC, Le Cesne A. Efficacy and safety of trabectedin in patients with advanced or metastatic liposarcoma or leiomyosarcoma after failure of prior anthracyclines and ifosfamide: results of a randomized phase II study of two different schedules. J Clin Oncol. 2009 Sep 1;27(25):4188-96. Epub 2009 Aug 3. PubMed PMID: 19652065.

39: Le Cesne A, Domont J, Cioffi A, Bonvalot S, Terrier P, Ray-Coquard I, Alfaro V, Lebedinsky C, Santabarbara P, Blay JY. Mapping the literature: role of trabectedin as a new chemotherapy option in advanced pretreated soft tissue sarcoma. Drugs Today (Barc). 2009 Jun;45(6):403-21. Review. PubMed PMID: 19649331.

40: Molinski T. Marine natural products. Clin Adv Hematol Oncol. 2009 Jun;7(6):383-5. PubMed PMID: 19606073.

41: Guirouilh-Barbat J, Antony S, Pommier Y. Zalypsis (PM00104) is a potent inducer of gamma-H2AX foci and reveals the importance of the C ring of trabectedin for transcription-coupled repair inhibition. Mol Cancer Ther. 2009 Jul;8(7):2007-14. Epub 2009 Jul 7. PubMed PMID: 19584237.

42: Guirouilh-Barbat J, Zhang YW, Pommier Y. Induction of glutathione-dependent DNA double-strand breaks by the novel anticancer drug brostallicin. Mol Cancer Ther. 2009 Jul;8(7):1985-94. Epub 2009 Jul 7. PubMed PMID: 19584235; PubMed Central PMCID: PMC2760303.

43: Tomillero A, Moral MA. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2009 May;31(4):263-98. PubMed PMID: 19557204.

44: Del Campo JM, Roszak A, Bidzinski M, Ciuleanu TE, Hogberg T, Wojtukiewicz MZ, Poveda A, Boman K, Westermann AM, Lebedinsky C; Yondelis Ovarian Cancer Group. Phase II randomized study of trabectedin given as two different every 3 weeks dose schedules (1.5 mg/m2 24 h or 1.3 mg/m2 3 h) to patients with relapsed, platinum-sensitive, advanced ovarian cancer. Ann Oncol. 2009 Nov;20(11):1794-802. Epub 2009 Jun 25. PubMed PMID: 19556318.

45: Boudou L, Baconnier M, Blay JY, Lombard-Bohas C, Cassier PA. Trabectedin for the management of soft-tissue sarcoma. Expert Rev Anticancer Ther. 2009 Jun;9(6):727-37. Review. PubMed PMID: 19496709.

46: McMeekin DS, Lisyanskaya A, Crispens M, Oza AM, Braly P, Doering D, Bayever E, Michiels B, Markman M. Single-agent trabectedin as second-line therapy of persistent or recurrent endometrial cancer: results of a multicenter phase II study. Gynecol Oncol. 2009 Aug;114(2):288-92. Epub 2009 May 23. PubMed PMID: 19476988.

47: Grosso F, Sanfilippo R, Virdis E, Piovesan C, Collini P, Dileo P, Morosi C, Tercero JC, Jimeno J, D'Incalci M, Gronchi A, Pilotti S, Casali PG. Trabectedin in myxoid liposarcomas (MLS): a long-term analysis of a single-institution series. Ann Oncol. 2009 Aug;20(8):1439-44. Epub 2009 May 22. PubMed PMID: 19465423.

48: Hollebecque A, Adenis A, Taieb S, Lebedinsky C, Penel N. Inadequacy of size-based response criteria to assess the efficacy of trabectedin among metastatic sarcoma patients. Invest New Drugs. 2010 Aug;28(4):529-30. Epub 2009 May 9. PubMed PMID: 19430728.

49: Leal JF, García-Hernández V, Moneo V, Domingo A, Bueren-Calabuig JA, Negri A, Gago F, Guillén-Navarro MJ, Avilés P, Cuevas C, García-Fernández LF, Galmarini CM. Molecular pharmacology and antitumor activity of Zalypsis in several human cancer cell lines. Biochem Pharmacol. 2009 Jul 15;78(2):162-70. Epub 2009 Apr 11. PubMed PMID: 19427997.

50: Vermeir M, Hemeryck A, Cuyckens F, Francesch A, Bockx M, Van Houdt J, Steemans K, Mannens G, Avilés P, De Coster R. In vitro studies on the metabolism of trabectedin (YONDELIS) in monkey and man, including human CYP reaction phenotyping. Biochem Pharmacol. 2009 May 15;77(10):1642-54. Epub 2009 Mar 10. PubMed PMID: 19426702.

51: Sessa C, Cresta S, Noberasco C, Capri G, Gallerani E, De Braud F, Zucchetti M, D'Incalci M, Locatelli A, Marsoni S, Corradino I, Minoia C, Zintl P, Gianni L. Phase I clinical and pharmacokinetic study of trabectedin and cisplatin in solid tumours. Eur J Cancer. 2009 Aug;45(12):2116-22. Epub 2009 May 4. PubMed PMID: 19419856.

52: Forouzesh B, Hidalgo M, Chu Q, Mita A, Mita M, Schwartz G, Jimeno J, Gómez J, Alfaro V, Lebedinsky C, Zintl P, Rowinsky EK. Phase I and pharmacokinetic study of trabectedin as a 1- or 3-hour infusion weekly in patients with advanced solid malignancies. Clin Cancer Res. 2009 May 15;15(10):3591-9. Epub 2009 May 5. PubMed PMID: 19417019.

53: Kurebayashi J. Possible treatment strategies for triple-negative breast cancer on the basis of molecular characteristics. Breast Cancer. 2009;16(4):275-80. Epub 2009 May 1. PubMed PMID: 19408071.

54: Amant F, Coosemans A, Renard V, Everaert E, Vergote I. Clinical outcome of ET-743 (Trabectedin; Yondelis) in high-grade uterine sarcomas: report on five patients and a review of the literature. Int J Gynecol Cancer. 2009 Feb;19(2):245-8. Review. PubMed PMID: 19396002.

55: Glaser KB, Mayer AM. A renaissance in marine pharmacology: from preclinical curiosity to clinical reality. Biochem Pharmacol. 2009 Sep 1;78(5):440-8. Epub 2009 Apr 22. PubMed PMID: 19393227.

56: Cuevas C, Francesch A. Development of Yondelis (trabectedin, ET-743). A semisynthetic process solves the supply problem. Nat Prod Rep. 2009 Mar;26(3):322-37. Epub 2009 Jan 7. Review. PubMed PMID: 19240944.

57: Beumer JH, Franke NE, Tolboom R, Buckle T, Rosing H, Lopez-Lazaro L, Schellens JH, Beijnen JH, van Tellingen O. Disposition and toxicity of trabectedin (ET-743) in wild-type and mdr1 gene (P-gp) knock-out mice. Invest New Drugs. 2010 Apr;28(2):145-55. Epub 2009 Feb 24. PubMed PMID: 19238326.

58: Schwarzbach MH, Hohenberger P. Current concepts in the management of retroperitoneal soft tissue sarcoma. Recent Results Cancer Res. 2009;179:301-19. Review. PubMed PMID: 19230548.

59: Forni C, Minuzzo M, Virdis E, Tamborini E, Simone M, Tavecchio M, Erba E, Grosso F, Gronchi A, Aman P, Casali P, D'Incalci M, Pilotti S, Mantovani R. Trabectedin (ET-743) promotes differentiation in myxoid liposarcoma tumors. Mol Cancer Ther. 2009 Feb;8(2):449-57. Epub 2009 Feb 3. PubMed PMID: 19190116.

60: Bailly C. Ready for a comeback of natural products in oncology. Biochem Pharmacol. 2009 May 1;77(9):1447-57. Epub 2008 Dec 31. PubMed PMID: 19161987.

61: Beumer JH, Lopez-Lazaro L, Schellens JH, Beijnen JH, van Tellingen O. Evaluation of human plasma protein binding of trabectedin (Yondelis, ET-743). Curr Clin Pharmacol. 2009 Jan;4(1):38-42. PubMed PMID: 19149499.

62: Christinat A, Leyvraz S. Role of trabectedin in the treatment of soft tissue sarcoma. Onco Targets Ther. 2009 Feb 18;2:105-13. PubMed PMID: 20616899; PubMed Central PMCID: PMC2886331.

63: Sessa C, Perotti A, Noberasco C, De Braud F, Gallerani E, Cresta S, Zucchetti M, Viganò L, Locatelli A, Jimeno J, Feilchenfeldt JW, D'Incalci M, Capri G, Ielmini N, Gianni L. Phase I clinical and pharmacokinetic study of trabectedin and doxorubicin in advanced soft tissue sarcoma and breast cancer. Eur J Cancer. 2009 May;45(7):1153-61. Epub 2008 Dec 27. PubMed PMID: 19114300.

64: Molinski TF, Dalisay DS, Lievens SL, Saludes JP. Drug development from marine natural products. Nat Rev Drug Discov. 2009 Jan;8(1):69-85. Epub 2008 Dec 19. Review. PubMed PMID: 19096380.

65: Barthomeuf C, Bourguet-Kondracki ML, Kornprobst JM. Marine metabolites overcoming or circumventing multidrug resistance mediated by ATP-dependent transporters: a new hope for patient with tumors resistant to conventional chemotherapy. Anticancer Agents Med Chem. 2008 Dec;8(8):886-903. Review. PubMed PMID: 19075571.

66: Ebada SS, Edrada RA, Lin W, Proksch P. Methods for isolation, purification and structural elucidation of bioactive secondary metabolites from marine invertebrates. Nat Protoc. 2008;3(12):1820-31. PubMed PMID: 18989260.

67: Blay JY, von Mehren M, Samuels BL, Fanucchi MP, Ray-Coquard I, Buckley B, Gilles L, Lebedinsky C, Elsayed YA, Le Cesne A. Phase I combination study of trabectedin and doxorubicin in patients with soft-tissue sarcoma. Clin Cancer Res. 2008 Oct 15;14(20):6656-62. PubMed PMID: 18927308; PubMed Central PMCID: PMC2777645.

68: Aune GJ, Takagi K, Sordet O, Guirouilh-Barbat J, Antony S, Bohr VA, Pommier Y. Von Hippel-Lindau-coupled and transcription-coupled nucleotide excision repair-dependent degradation of RNA polymerase II in response to trabectedin. Clin Cancer Res. 2008 Oct 15;14(20):6449-55. PubMed PMID: 18927284; PubMed Central PMCID: PMC2662138.

69: Duan Z, Choy E, Jimeno JM, Cuevas Cdel M, Mankin HJ, Hornicek FJ. Diverse cross-resistance phenotype to ET-743 and PM00104 in multi-drug resistant cell lines. Cancer Chemother Pharmacol. 2009 May;63(6):1121-9. Epub 2008 Oct 1. PubMed PMID: 18828019.

70: Vermeulen W, Filliers W, García C, Manzanaro S, Montalvo D, Polanco C, Spillemaeckers F, Van Hoof B, Winderickx G, Somers I, Rodriguez-Campos I. Structure elucidation and 1H/13C NMR spectral assignments of four trabectedin related compounds. Magn Reson Chem. 2008 Dec;46(12):1198-202. PubMed PMID: 18821578.

71: Cassier PA, Dufresne A, Blay JY, Fayette J. Trabectedin and its potential in the treatment of soft tissue sarcoma. Ther Clin Risk Manag. 2008 Feb;4(1):109-16. PubMed PMID: 18728699; PubMed Central PMCID: PMC2503645.

72: Zhang JY, Fu LW. [Advance of several types of important marine antitumor drugs]. Yao Xue Xue Bao. 2008 May;43(5):435-42. Review. Chinese. PubMed PMID: 18717327.

73: Fishlock D, Williams RM. Synthetic studies on Et-743. Assembly of the pentacyclic core and a formal total synthesis. J Org Chem. 2008 Dec 19;73(24):9594-600. PubMed PMID: 18687003; PubMed Central PMCID: PMC2736329.

74: Guirouilh-Barbat J, Redon C, Pommier Y. Transcription-coupled DNA double-strand breaks are mediated via the nucleotide excision repair and the Mre11-Rad50-Nbs1 complex. Mol Biol Cell. 2008 Sep;19(9):3969-81. Epub 2008 Jul 16. PubMed PMID: 18632984; PubMed Central PMCID: PMC2526702.

75: Kopp HG, Patel S, Brücher B, Hartmann JT. Potential combination chemotherapy approaches for advanced adult-type soft-tissue sarcoma. Am J Clin Dermatol. 2008;9(4):207-17. Review. PubMed PMID: 18572972.

76: Schöffski P, Dumez H, Wolter P, Stefan C, Wozniak A, Jimeno J, Van Oosterom AT. Clinical impact of trabectedin (ecteinascidin-743) in advanced/metastatic soft tissue sarcoma. Expert Opin Pharmacother. 2008 Jun;9(9):1609-18. Review. PubMed PMID: 18518789.

77: Thornton K. Chemotherapeutic management of soft tissue sarcoma. Surg Clin North Am. 2008 Jun;88(3):647-60, viii. Review. PubMed PMID: 18514704.

78: Romero J, Zapata I, Córdoba S, Jimeno JM, López-Martín JA, Tercero JC, De La Torre A, Vargas JA, Molerón R, Sánchez-Prieto R. In vitro radiosensitisation by trabectedin in human cancer cell lines. Eur J Cancer. 2008 Aug;44(12):1726-33. Epub 2008 May 22. PubMed PMID: 18501589.

79: von Mehren M, Schilder RJ, Cheng JD, Temmer E, Cardoso TM, Renshaw FG, Bayever E, Zannikos P, Yuan Z, Cohen RB. A phase I study of the safety and pharmacokinetics of trabectedin in combination with pegylated liposomal doxorubicin in patients with advanced malignancies. Ann Oncol. 2008 Oct;19(10):1802-9. Epub 2008 May 22. PubMed PMID: 18497430; PubMed Central PMCID: PMC2598415.

80: Casado JA, Río P, Marco E, García-Hernández V, Domingo A, Pérez L, Tercero JC, Vaquero JJ, Albella B, Gago F, Bueren JA. Relevance of the Fanconi anemia pathway in the response of human cells to trabectedin. Mol Cancer Ther. 2008 May;7(5):1309-18. PubMed PMID: 18483318.

81: Dean-Colomb W, Esteva FJ. Emerging agents in the treatment of anthracycline- and taxane-refractory metastatic breast cancer. Semin Oncol. 2008 Apr;35(2 Suppl 2):S31-8; quiz S40. Review. PubMed PMID: 18410797.

82: Apice G, Milano A, Bruni GS, Iaffaioli RV, Caponigro F. Medical treatment of gastrointestinal stromal tumors: state of the art and future perspectives. Rev Recent Clin Trials. 2006 Jan;1(1):35-42. Review. PubMed PMID: 18393778.

83: Bayés M, Rabasseda X. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2008 Jan-Feb;30(1):67-99. PubMed PMID: 18389098.

84: Messersmith WA, Jimeno A, Ettinger D, Laheru D, Brahmer J, Lansey D, Khan Y, Donehower RC, Elsayed Y, Zannikos P, Hidalgo M. Phase I trial of weekly trabectedin (ET-743) and gemcitabine in patients with advanced solid tumors. Cancer Chemother Pharmacol. 2008 Dec;63(1):181-8. Epub 2008 Apr 1. PubMed PMID: 18379785.

85: Dinh P, Harnett P, Piccart-Gebhart MJ, Awada A. New therapies for ovarian cancer: cytotoxics and molecularly targeted agents. Crit Rev Oncol Hematol. 2008 Aug;67(2):103-12. Epub 2008 Mar 14. Review. PubMed PMID: 18342536.

86: Wright BJ, Chan C, Danishefsky SJ. Synthesis and cytotoxic evaluation of some cribrostatin-ecteinascidin analogues. J Nat Prod. 2008 Mar;71(3):409-14. Epub 2008 Feb 16. PubMed PMID: 18278868.

87: Tavecchio M, Simone M, Erba E, Chiolo I, Liberi G, Foiani M, D'Incalci M, Damia G. Role of homologous recombination in trabectedin-induced DNA damage. Eur J Cancer. 2008 Mar;44(4):609-18. Epub 2008 Feb 19. PubMed PMID: 18243687.

88: Bayés M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2007 Nov;29(9):625-55. PubMed PMID: 18193114.

89: Lee JK, Leslie EM, Zamek-Gliszczynski MJ, Brouwer KL. Modulation of trabectedin (ET-743) hepatobiliary disposition by multidrug resistance-associated proteins (Mrps) may prevent hepatotoxicity. Toxicol Appl Pharmacol. 2008 Apr 1;228(1):17-23. Epub 2007 Dec 3. PubMed PMID: 18191164; PubMed Central PMCID: PMC2572823.

90: Stevens EV, Nishizuka S, Antony S, Reimers M, Varma S, Young L, Munson PJ, Weinstein JN, Kohn EC, Pommier Y. Predicting cisplatin and trabectedin drug sensitivity in ovarian and colon cancers. Mol Cancer Ther. 2008 Jan;7(1):10-8. Epub 2008 Jan 9. PubMed PMID: 18187810.

91: Tavecchio M, Natoli C, Ubezio P, Erba E, D'Incalci M. Dynamics of cell cycle phase perturbations by trabectedin (ET-743) in nucleotide excision repair (NER)-deficient and NER-proficient cells, unravelled by a novel mathematical simulation approach. Cell Prolif. 2007 Dec;40(6):885-904. PubMed PMID: 18021177.

92: Krasner CN, McMeekin DS, Chan S, Braly PS, Renshaw FG, Kaye S, Provencher DM, Campos S, Gore ME. A Phase II study of trabectedin single agent in patients with recurrent ovarian cancer previously treated with platinum-based regimens. Br J Cancer. 2007 Dec 17;97(12):1618-24. Epub 2007 Nov 13. PubMed PMID: 18000504; PubMed Central PMCID: PMC2360276.

93: Carter NJ, Keam SJ. Trabectedin : a review of its use in the management of soft tissue sarcoma and ovarian cancer. Drugs. 2007;67(15):2257-76. Review. PubMed PMID: 17927287.

94: Fetterly GJ, Owen JS, Stuyckens K, Passarell JA, Zannikos P, Soto-Matos A, Izquierdo MA, Perez-Ruixo JJ. Semimechanistic pharmacokinetic/pharmacodynamic model for hepatoprotective effect of dexamethasone on transient transaminitis after trabectedin (ET-743) treatment. Cancer Chemother Pharmacol. 2008 Jun;62(1):135-47. Epub 2007 Oct 9. PubMed PMID: 17922277.

95: D'Incalci M, Brunelli D, Marangon E, Simone M, Tavecchio M, Gescher A, Mantovani R. Modulation of gene transcription by natural products--a viable anticancer strategy. Curr Pharm Des. 2007;13(27):2744-50. Review. PubMed PMID: 17897020.

96: Perez-Ruixo JJ, Zannikos P, Hirankarn S, Stuyckens K, Ludwig EA, Soto-Matos A, Lopez-Lazaro L, Owen JS. Population pharmacokinetic meta-analysis of trabectedin (ET-743, Yondelis) in cancer patients. Clin Pharmacokinet. 2007;46(10):867-84. PubMed PMID: 17854236.

97: Schöffski P, Wolter P, Clement P, Sciot R, De Wever I, Wozniak A, Stefan C, Dumez H. Trabectedin (ET-743): evaluation of its use in advanced soft-tissue sarcoma. Future Oncol. 2007 Aug;3(4):381-92. Review. PubMed PMID: 17661712.

98: Soares DG, Escargueil AE, Poindessous V, Sarasin A, de Gramont A, Bonatto D, Henriques JA, Larsen AK. Replication and homologous recombination repair regulate DNA double-strand break formation by the antitumor alkylator ecteinascidin 743. Proc Natl Acad Sci U S A. 2007 Aug 7;104(32):13062-7. Epub 2007 Jul 26. PubMed PMID: 17656556; PubMed Central PMCID: PMC1941813.

99: Roylance R, Seddon B, McTiernan A, Sykes K, Daniels S, Whelan J. Experience of the use of trabectedin (ET-743, Yondelis) in 21 patients with pre-treated advanced sarcoma from a single centre. Clin Oncol (R Coll Radiol). 2007 Oct;19(8):572-6. Epub 2007 Jul 10. PubMed PMID: 17624747.

100: von Mehren M. Trabectedin--a targeted chemotherapy? Lancet Oncol. 2007 Jul;8(7):565-7. PubMed PMID: 17613417.

101: Skorupa A, Beldner M, Kraft A, Montero AJ. Fatal rhabdomyolysis as a complication of ET-743 (Yondelis) chemotherapy for sarcoma. Cancer Biol Ther. 2007 Jul;6(7):1015-7. PubMed PMID: 17611408.

102: Hing J, Perez-Ruixo JJ, Stuyckens K, Soto-Matos A, Lopez-Lazaro L, Zannikos P. Mechanism-based pharmacokinetic/pharmacodynamic meta-analysis of trabectedin (ET-743, Yondelis) induced neutropenia. Clin Pharmacol Ther. 2008 Jan;83(1):130-43. Epub 2007 Jun 27. PubMed PMID: 17597713.

103: Grosso F, Jones RL, Demetri GD, Judson IR, Blay JY, Le Cesne A, Sanfilippo R, Casieri P, Collini P, Dileo P, Spreafico C, Stacchiotti S, Tamborini E, Tercero JC, Jimeno J, D'Incalci M, Gronchi A, Fletcher JA, Pilotti S, Casali PG. Efficacy of trabectedin (ecteinascidin-743) in advanced pretreated myxoid liposarcomas: a retrospective study. Lancet Oncol. 2007 Jul;8(7):595-602. PubMed PMID: 17586092.

104: Paz-Ares L, Rivera-Herreros F, Díaz-Rubio E, García M, Casado E, Cubedo R, Gravalos C, Alfaro V, Gómez J, Izquierdo MA, Tabernero J. Phase II study of trabectedin in pretreated patients with advanced colorectal cancer. Clin Colorectal Cancer. 2007 May;6(7):522-8. PubMed PMID: 17553201.

105: Bayés M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2007 Jan-Feb;29(1):53-71. PubMed PMID: 17344945.

106: von Mehren M. New therapeutics for soft-tissue sarcomas in adults. Oncology (Williston Park). 2007 Jan;21(1):123-6. PubMed PMID: 17313160.

107: Bayes M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2006 Dec;28(10):719-40. PubMed PMID: 17235418.

108: Marco E, David-Cordonnier MH, Bailly C, Cuevas C, Gago F. Further insight into the DNA recognition mechanism of trabectedin from the differential affinity of its demethylated analogue ecteinascidin ET729 for the triplet DNA binding site CGA. J Med Chem. 2006 Nov 16;49(23):6925-9. PubMed PMID: 17154523.

109: Beumer JH, Rademaker-Lakhai JM, Rosing H, Hillebrand MJ, Bosch TM, Lopez-Lazaro L, Schellens JH, Beijnen JH. Metabolism of trabectedin (ET-743, Yondelis) in patients with advanced cancer. Cancer Chemother Pharmacol. 2007 May;59(6):825-37. Epub 2006 Sep 20. PubMed PMID: 16988825.

110: Trabectedin: Ecteinascidin 743, Ecteinascidin-743, ET 743, ET-743, NSC 684766. Drugs R D. 2006;7(5):317-28. Review. PubMed PMID: 16922593.

111: Herrero AB, Martín-Castellanos C, Marco E, Gago F, Moreno S. Cross-talk between nucleotide excision and homologous recombination DNA repair pathways in the mechanism of action of antitumor trabectedin. Cancer Res. 2006 Aug 15;66(16):8155-62. PubMed PMID: 16912194.

112: Moneo V, Serelde BG, Fominaya J, Leal JF, Blanco-Aparicio C, Romero L, Sánchez-Beato M, Cigudosa JC, Tercero JC, Piris MA, Jimeno J, Carnero A. Extreme sensitivity to Yondelis (Trabectedin, ET-743) in low passaged sarcoma cell lines correlates with mutated p53. J Cell Biochem. 2007 Feb 1;100(2):339-48. PubMed PMID: 16888811.

113: Fishlock D, Williams RM. Synthetic studies on Et-743. Asymmetric, stereocontrolled construction of the tetrahydroisoquinoline core via radical cyclization on a glyoxalimine. Org Lett. 2006 Jul 20;8(15):3299-301. PubMed PMID: 16836390.

114: Tewari D, Saffari B, Cowan C, Wallick AC, Koontz MZ, Monk BJ. Activity of trabectedin (ET-743, Yondelis) in metastatic uterine leiomyosarcoma. Gynecol Oncol. 2006 Sep;102(3):421-4. Epub 2006 Jun 23. PubMed PMID: 16797679.

115: Newman JC, Bailey AD, Weiner AM. Cockayne syndrome group B protein (CSB) plays a general role in chromatin maintenance and remodeling. Proc Natl Acad Sci U S A. 2006 Jun 20;103(25):9613-8. Epub 2006 Jun 13. PubMed PMID: 16772382; PubMed Central PMCID: PMC1480455.

116: Grosso F, Dileo P, Sanfilippo R, Stacchiotti S, Bertulli R, Piovesan C, Jimeno J, D'Incalci M, Gescher A, Casali PG. Steroid premedication markedly reduces liver and bone marrow toxicity of trabectedin in advanced sarcoma. Eur J Cancer. 2006 Jul;42(10):1484-90. Epub 2006 Jun 5. PubMed PMID: 16737808.

117: Zelek L, Yovine A, Brain E, Turpin F, Taamma A, Riofrio M, Spielmann M, Jimeno J, Misset JL. A phase II study of Yondelis (trabectedin, ET-743) as a 24-h continuous intravenous infusion in pretreated advanced breast cancer. Br J Cancer. 2006 Jun 5;94(11):1610-4. PubMed PMID: 16736024; PubMed Central PMCID: PMC2361304.

118: Fayette J, Coquard IR, Alberti L, Boyle H, Méeus P, Decouvelaere AV, Thiesse P, Sunyach MP, Ranchère D, Blay JY. ET-743: a novel agent with activity in soft-tissue sarcomas. Curr Opin Oncol. 2006 Jul;18(4):347-53. Review. PubMed PMID: 16721129.

119: O'Hanlon LH. Scientists are searching the seas for cancer drugs. J Natl Cancer Inst. 2006 May 17;98(10):662-3. PubMed PMID: 16705115.

120: Takahashi Y, Fuwa H, Kaneko A, Sasaki M, Yokoshima S, Koizumi H, Takebe T, Kan T, Iwatsubo T, Tomita T, Natsugari H, Fukuyama T. Novel gamma-secretase inhibitors discovered by library screening of in-house synthetic natural product intermediates. Bioorg Med Chem Lett. 2006 Jul 15;16(14):3813-6. Epub 2006 May 8. PubMed PMID: 16682195.

121: Manning T, Rhodes E, Loftis R, Phillips D, Demaria D, Newman D, Rudloe J. ET743: Chemical analysis of the sea squirt Ecteinascidia turbinata ecosystem. Nat Prod Res. 2006 May 10;20(5):461-73. PubMed PMID: 16644544.

122: Bayes M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2006 Mar;28(2):121-42. PubMed PMID: 16636723.

123: Beumer JH, Buckle T, Ouwehand M, Franke NE, Lopez-Lazaro L, Schellens JH, Beijnen JH, van Tellingen O. Trabectedin (ET-743, Yondelis) is a substrate for P-glycoprotein, but only high expression of P-glycoprotein confers the multidrug resistance phenotype. Invest New Drugs. 2007 Feb;25(1):1-7. PubMed PMID: 16633714.

124: Zheng S, Chan C, Furuuchi T, Wright BJ, Zhou B, Guo J, Danishefsky SJ. Stereospecific formal total synthesis of ecteinascidin 743. Angew Chem Int Ed Engl. 2006 Mar 3;45(11):1754-9. PubMed PMID: 16496274.

125: Sabbatini P. New agents and new formulations for the treatment of ovarian cancer. Clin Adv Hematol Oncol. 2005 Nov;3(11):840-2. PubMed PMID: 16491624.

126: Fayette J, Méeus P, Sunyach MP, Thiesse P, Ray Coquard I, Blay JY. [News of the year 2005 in sarcomas]. Bull Cancer. 2006 Jan 1;93(1):83-9. Review. French. PubMed PMID: 16455510.

127: Chen J, Chen X, Bois-Choussy M, Zhu J. Total synthesis of ecteinascidin 743. J Am Chem Soc. 2006 Jan 11;128(1):87-9. PubMed PMID: 16390134.

128: Brandon EF, Sparidans RW, Guijt KJ, Löwenthal S, Meijerman I, Beijnen JH, Schellens JH. In vitro characterization of the human biotransformation and CYP reaction phenotype of ET-743 (Yondelis, Trabectidin), a novel marine anti-cancer drug. Invest New Drugs. 2006 Jan;24(1):3-14. PubMed PMID: 16379042.

129: Fayette J, Coquard IR, Alberti L, Ranchère D, Boyle H, Blay JY. ET-743: a novel agent with activity in soft tissue sarcomas. Oncologist. 2005 Nov-Dec;10(10):827-32. Review. PubMed PMID: 16314293.

130: David-Cordonnier MH, Gajate C, Olmea O, Laine W, de la Iglesia-Vicente J, Perez C, Cuevas C, Otero G, Manzanares I, Bailly C, Mollinedo F. DNA and non-DNA targets in the mechanism of action of the antitumor drug trabectedin. Chem Biol. 2005 Nov;12(11):1201-10. PubMed PMID: 16298299.

131: Manara MC, Perdichizzi S, Serra M, Pierini R, Benini S, Hattinger CM, Astolfi A, Bagnati R, D'Incalci M, Picci P, Scotlandi K. The molecular mechanisms responsible for resistance to ET-743 (Trabectidin; Yondelis) in the Ewing's sarcoma cell line, TC-71. Int J Oncol. 2005 Dec;27(6):1605-16. PubMed PMID: 16273217.

132: Bayes M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2005 Jul-Aug;27(6):411-61. PubMed PMID: 16179960.

133: Brandon EF, Meijerman I, Klijn JS, den Arend D, Sparidans RW, Lázaro LL, Beijnen JH, Schellens JH. In-vitro cytotoxicity of ET-743 (Trabectedin, Yondelis), a marine anti-cancer drug, in the Hep G2 cell line: influence of cytochrome P450 and phase II inhibition, and cytochrome P450 induction. Anticancer Drugs. 2005 Oct;16(9):935-43. PubMed PMID: 16162970.

134: Marco E, Gago F. DNA structural similarity in the 2:1 complexes of the antitumor drugs trabectedin (Yondelis) and chromomycin A3 with an oligonucleotide sequence containing two adjacent TGG binding sites on opposing strands. Mol Pharmacol. 2005 Dec;68(6):1559-67. Epub 2005 Sep 8. PubMed PMID: 16150929.

135: Beumer JH, Rademaker-Lakhai JM, Rosing H, Lopez-Lazaro L, Beijnen JH, Schellens JH. Trabectedin (Yondelis, formerly ET-743), a mass balance study in patients with advanced cancer. Invest New Drugs. 2005 Oct;23(5):429-36. PubMed PMID: 16133794.

136: Garcia-Carbonero R, Supko JG, Maki RG, Manola J, Ryan DP, Harmon D, Puchalski TA, Goss G, Seiden MV, Waxman A, Quigley MT, Lopez T, Sancho MA, Jimeno J, Guzman C, Demetri GD. Ecteinascidin-743 (ET-743) for chemotherapy-naive patients with advanced soft tissue sarcomas: multicenter phase II and pharmacokinetic study. J Clin Oncol. 2005 Aug 20;23(24):5484-92. PubMed PMID: 16110008.

137: Verweij J. Ecteinascidin-743 (ET-743): early test or effective treatment in soft tissue sarcomas? J Clin Oncol. 2005 Aug 20;23(24):5420-3. PubMed PMID: 16109999.

138: Riccardi A, Meco D, Ubezio P, Mazzarella G, Marabese M, Faircloth GT, Jimeno J, D'Incalci M, Riccardi R. Combination of trabectedin and irinotecan is highly effective in a human rhabdomyosarcoma xenograft. Anticancer Drugs. 2005 Sep;16(8):811-5. PubMed PMID: 16096428.

139: Bayes M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2005 May;27(4):265-84. PubMed PMID: 16082427.

140: Bayés M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2005 Jun;27(5):331-72. PubMed PMID: 16082422.

141: Minuzzo M, Ceribelli M, Pitarque-Martì M, Borrelli S, Erba E, DiSilvio A, D'Incalci M, Mantovani R. Selective effects of the anticancer drug Yondelis (ET-743) on cell-cycle promoters. Mol Pharmacol. 2005 Nov;68(5):1496-503. Epub 2005 Jun 16. PubMed PMID: 15961672.

142: Therasse P, Le Cesne A, Van Glabbeke M, Verweij J, Judson I; for the EORTC Soft Tissue and Bone Sarcoma Group. RECIST vs. WHO: prospective comparison of response criteria in an EORTC phase II clinical trial investigating ET-743 in advanced soft tissue sarcoma. Eur J Cancer. 2005 Jul;41(10):1426-30. PubMed PMID: 15919202.

143: Soares DG, Poletto NP, Bonatto D, Salvador M, Schwartsmann G, Henriques JA. Low cytotoxicity of ecteinascidin 743 in yeast lacking the major endonucleolytic enzymes of base and nucleotide excision repair pathways. Biochem Pharmacol. 2005 Jul 1;70(1):59-69. PubMed PMID: 15913564.

144: Chen X, Chen J, De Paolis M, Zhu J. Synthetic studies toward ecteinascidin 743. J Org Chem. 2005 May 27;70(11):4397-408. PubMed PMID: 15903318.

145: Martínez N, Sánchez-Beato M, Carnero A, Moneo V, Tercero JC, Fernández I, Navarrete M, Jimeno J, Piris MA. Transcriptional signature of Ecteinascidin 743 (Yondelis, Trabectedin) in human sarcoma cells explanted from chemo-naive patients. Mol Cancer Ther. 2005 May;4(5):814-23. PubMed PMID: 15897246.

146: Allavena P, Signorelli M, Chieppa M, Erba E, Bianchi G, Marchesi F, Olimpio CO, Bonardi C, Garbi A, Lissoni A, de Braud F, Jimeno J, D'Incalci M. Anti-inflammatory properties of the novel antitumor agent yondelis (trabectedin): inhibition of macrophage differentiation and cytokine production. Cancer Res. 2005 Apr 1;65(7):2964-71. PubMed PMID: 15805300.

147: Sessa C, De Braud F, Perotti A, Bauer J, Curigliano G, Noberasco C, Zanaboni F, Gianni L, Marsoni S, Jimeno J, D'Incalci M, Dall'ó E, Colombo N. Trabectedin for women with ovarian carcinoma after treatment with platinum and taxanes fails. J Clin Oncol. 2005 Mar 20;23(9):1867-74. PubMed PMID: 15774779.

148: Beumer JH, Schellens JH, Beijnen JH. Hepatotoxicity and metabolism of trabectedin: a literature review. Pharmacol Res. 2005 May;51(5):391-8. Review. PubMed PMID: 15749453.

149: Simmons TL, Andrianasolo E, McPhail K, Flatt P, Gerwick WH. Marine natural products as anticancer drugs. Mol Cancer Ther. 2005 Feb;4(2):333-42. Review. PubMed PMID: 15713904.

150: Lau L, Supko JG, Blaney S, Hershon L, Seibel N, Krailo M, Qu W, Malkin D, Jimeno J, Bernstein M, Baruchel S. A phase I and pharmacokinetic study of ecteinascidin-743 (Yondelis) in children with refractory solid tumors. A Children's Oncology Group study. Clin Cancer Res. 2005 Jan 15;11(2 Pt 1):672-7. PubMed PMID: 15701855.

151: D'Incalci M, Simone M, Tavecchio M, Damia G, Garbi A, Erba E. New drugs from the sea. J Chemother. 2004 Nov;16 Suppl 4:86-9. Review. PubMed PMID: 15688619.

152: Erba E, Cavallaro E, Damia G, Mantovani R, Di Silvio A, Di Francesco AM, Riccardi R, Cuevas C, Faircloth GT, D'Incalci M. The unique biological features of the marine product Yondelis (ET-743, trabectedin) are shared by its analog ET-637, which lacks the C ring. Oncol Res. 2004;14(11-12):579-87. PubMed PMID: 15666999.

153: Marchini S, Marrazzo E, Bonomi R, Chiorino G, Zaffaroni M, Weissbach L, Hornicek FJ, Broggini M, Faircloth GT, D'Incalci M. Molecular characterisation of two human cancer cell lines selected in vitro for their chemotherapeutic drug resistance to ET-743. Eur J Cancer. 2005 Jan;41(2):323-33. PubMed PMID: 15661559.

154: Le Cesne A, Blay JY, Judson I, Van Oosterom A, Verweij J, Radford J, Lorigan P, Rodenhuis S, Ray-Coquard I, Bonvalot S, Collin F, Jimeno J, Di Paola E, Van Glabbeke M, Nielsen OS. Phase II study of ET-743 in advanced soft tissue sarcomas: a European Organisation for the Research and Treatment of Cancer (EORTC) soft tissue and bone sarcoma group trial. J Clin Oncol. 2005 Jan 20;23(3):576-84. Erratum in: J Clin Oncol. 2005 Aug 1;23(22):5276. PubMed PMID: 15659504.

155: Hartmann JT, Patel S. Recent developments in salvage chemotherapy for patients with metastatic soft tissue sarcoma. Drugs. 2005;65(2):167-78. Review. PubMed PMID: 15631540.

156: Bayés M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2004 Oct;26(8):639-63. PubMed PMID: 15605126.

157: Dziegielewska B, Kowalski D, Beerman TA. SV40 DNA replication inhibition by the monofunctional DNA alkylator Et743. Biochemistry. 2004 Nov 9;43(44):14228-37. PubMed PMID: 15518573.

158: Wang Y, Liu ZZ, Chen SZ, Liang XT. [Progress in the studies on antitumor natural product ecteinascidin-743]. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2004 Aug;26(4):474-8. Review. Chinese. PubMed PMID: 15379280.

159: Bayes M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2004 Jul-Aug;26(6):473-503. PubMed PMID: 15349141.

160: Donald S, Verschoyle RD, Greaves P, Colombo T, Zucchetti M, Falcioni C, Zaffaroni M, D'Incalci M, Manson MM, Jimeno J, Steward WP, Gescher AJ. Dietary agent indole-3-carbinol protects female rats against the hepatotoxicity of the antitumor drug ET-743 (trabectidin) without compromising efficacy in a rat mammary carcinoma. Int J Cancer. 2004 Oct 10;111(6):961-7. PubMed PMID: 15300810.

161: Blay JY, Le Cesne A, Verweij J, Scurr M, Seynaeve C, Bonvalot S, Hogendoorn P, Jimeno J, Evrard V, van Glabbeke M, Judson I. A phase II study of ET-743/trabectedin ('Yondelis') for patients with advanced gastrointestinal stromal tumours. Eur J Cancer. 2004 Jun;40(9):1327-31. PubMed PMID: 15177491.

162: Bayés M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2004 Apr;26(3):211-44. PubMed PMID: 15148527.

163: Stokvis E, Rosing H, López-Lázaro L, Beijnen JH. Simple and sensitive liquid chromatographic quantitative analysis of the novel marine anticancer drug Yondelis (ET-743, trabectedin) in human plasma using column switching and tandem mass spectrometric detection. J Mass Spectrom. 2004 Apr;39(4):431-6. PubMed PMID: 15103657.

164: Garcia-Carbonero R, Supko JG, Manola J, Seiden MV, Harmon D, Ryan DP, Quigley MT, Merriam P, Canniff J, Goss G, Matulonis U, Maki RG, Lopez T, Puchalski TA, Sancho MA, Gomez J, Guzman C, Jimeno J, Demetri GD. Phase II and pharmacokinetic study of ecteinascidin 743 in patients with progressive sarcomas of soft tissues refractory to chemotherapy. J Clin Oncol. 2004 Apr 15;22(8):1480-90. PubMed PMID: 15084621.

165: Jimeno J, López-Martín JA, Ruiz-Casado A, Izquierdo MA, Scheuer PJ, Rinehart K. Progress in the clinical development of new marine-derived anticancer compounds. Anticancer Drugs. 2004 Apr;15(4):321-9. Review. PubMed PMID: 15057135.

166: Scotto KW, Johnson RA. Transcription of the multidrug resistance gene MDR1: a therapeutic target. Mol Interv. 2001 Jun;1(2):117-25. Review. PubMed PMID: 14993331.

167: Yovine A, Riofrio M, Blay JY, Brain E, Alexandre J, Kahatt C, Taamma A, Jimeno J, Martin C, Salhi Y, Cvitkovic E, Misset JL. Phase II study of ecteinascidin-743 in advanced pretreated soft tissue sarcoma patients. J Clin Oncol. 2004 Mar 1;22(5):890-9. PubMed PMID: 14990645.

168: Bayés M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2004 Jan-Feb;26(1):53-84. Review. PubMed PMID: 14988742.

169: Bayes M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2003 Nov;25(9):747-71. PubMed PMID: 14685303.

170: Simoens C, Korst AE, De Pooter CM, Lambrechts HA, Pattyn GG, Faircloth GT, Lardon F, Vermorken JB. In vitro interaction between ecteinascidin 743 (ET-743) and radiation, in relation to its cell cycle effects. Br J Cancer. 2003 Dec 15;89(12):2305-11. PubMed PMID: 14676811; PubMed Central PMCID: PMC2395275.

171: Donald S, Verschoyle RD, Greaves P, Orr S, Jimeno J, Gescher AJ. Comparison of four modulators of drug metabolism as protectants against the hepatotoxicity of the novel antitumor drug yondelis (ET-743) in the female rat and in hepatocytes in vitro. Cancer Chemother Pharmacol. 2004 Apr;53(4):305-12. Epub 2003 Dec 11. PubMed PMID: 14669039.

172: Shao L, Kasanov J, Hornicek FJ, Morii T, Fondren G, Weissbach L. Ecteinascidin-743 drug resistance in sarcoma cells: transcriptional and cellular alterations. Biochem Pharmacol. 2003 Dec 15;66(12):2381-95. PubMed PMID: 14637196.

173: Gómez SG, Bueren JA, Faircloth G, Albella B. Use of CFU-GM assay for prediction of human maximum tolerated dose of a new antitumoral drug: Yondelis (ET-743). Toxicol In Vitro. 2003 Oct-Dec;17(5-6):671-4. PubMed PMID: 14599461.

174: Tognon G, Frapolli R, Zaffaroni M, Erba E, Zucchetti M, Faircloth GT, D'Incalci M. Fetal bovine serum, but not human serum, inhibits the in vitro cytotoxicity of ET-743 (Yondelis, trabectedin), an example of potential problems for extrapolation of active drug concentrations from in vitro studies. Cancer Chemother Pharmacol. 2004 Jan;53(1):89-90. Epub 2003 Oct 28. PubMed PMID: 14586558.

175: Gómez SG, Bueren JA, Faircloth GT, Jimeno J, Albella B. In vitro toxicity of three new antitumoral drugs (trabectedin, aplidin, and kahalalide F) on hematopoietic progenitors and stem cells. Exp Hematol. 2003 Nov;31(11):1104-11. PubMed PMID: 14585376.

176: von Mehren M. New therapeutic strategies for soft tissue sarcomas. Curr Treat Options Oncol. 2003 Dec;4(6):441-51. Review. PubMed PMID: 14585225.

177: D'Incalci M, Jimeno J. Preclinical and clinical results with the natural marine product ET-743. Expert Opin Investig Drugs. 2003 Nov;12(11):1843-53. Review. PubMed PMID: 14585059.

178: Amador ML, Jimeno J, Paz-Ares L, Cortes-Funes H, Hidalgo M. Progress in the development and acquisition of anticancer agents from marine sources. Ann Oncol. 2003 Nov;14(11):1607-15. Review. PubMed PMID: 14581267.

179: Donald S, Verschoyle RD, Greaves P, Gant TW, Colombo T, Zaffaroni M, Frapolli R, Zucchetti M, D'Incalci M, Meco D, Riccardi R, Lopez-Lazaro L, Jimeno J, Gescher AJ. Complete protection by high-dose dexamethasone against the hepatotoxicity of the novel antitumor drug yondelis (ET-743) in the rat. Cancer Res. 2003 Sep 15;63(18):5902-8. PubMed PMID: 14522916.

180: Burton A. Orphan anticancer drug rejected. Lancet Oncol. 2003 Sep;4(9):524. PubMed PMID: 12965283.

181: van Kesteren Ch, de Vooght MM, López-Lázaro L, Mathôt RA, Schellens JH, Jimeno JM, Beijnen JH. Yondelis (trabectedin, ET-743): the development of an anticancer agent of marine origin. Anticancer Drugs. 2003 Aug;14(7):487-502. Review. PubMed PMID: 12960733.

182: Bayés M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2003 Jul-Aug;25(6):483-506. PubMed PMID: 12949633.

183: D'Incalci M, Colombo T, Ubezio P, Nicoletti I, Giavazzi R, Erba E, Ferrarese L, Meco D, Riccardi R, Sessa C, Cavallini E, Jimeno J, Faircloth GT. The combination of yondelis and cisplatin is synergistic against human tumor xenografts. Eur J Cancer. 2003 Sep;39(13):1920-6. PubMed PMID: 12932672.

184: Twelves C, Hoekman K, Bowman A, Vermorken JB, Anthoney A, Smyth J, van Kesteren C, Beijnen JH, Uiters J, Wanders J, Gomez J, Guzmán C, Jimeno J, Hanauske A. Phase I and pharmacokinetic study of Yondelis (Ecteinascidin-743; ET-743) administered as an infusion over 1 h or 3 h every 21 days in patients with solid tumours. Eur J Cancer. 2003 Sep;39(13):1842-51. PubMed PMID: 12932661.

185: Smyth JF. Rationale for drug combinations. Eur J Cancer. 2003 Sep;39(13):1816-7. PubMed PMID: 12932657.

186: Mendola D. Aquaculture of three phyla of marine invertebrates to yield bioactive metabolites: process developments and economics. Biomol Eng. 2003 Jul;20(4-6):441-58. PubMed PMID: 12919831.

187: Laverdiere C, Kolb EA, Supko JG, Gorlick R, Meyers PA, Maki RG, Wexler L, Demetri GD, Healey JH, Huvos AG, Goorin AM, Bagatell R, Ruiz-Casado A, Guzman C, Jimeno J, Harmon D. Phase II study of ecteinascidin 743 in heavily pretreated patients with recurrent osteosarcoma. Cancer. 2003 Aug 15;98(4):832-40. PubMed PMID: 12910529.

188: Schwartsmann G, Da Rocha AB, Mattei J, Lopes R. Marine-derived anticancer agents in clinical trials. Expert Opin Investig Drugs. 2003 Aug;12(8):1367-83. PubMed PMID: 12882622.

189: Louneva N, Saitta B, Herrick DJ, Jimenez SA. Transcriptional inhibition of type I collagen gene expression in scleroderma fibroblasts by the antineoplastic drug ecteinascidin 743. J Biol Chem. 2003 Oct 10;278(41):40400-7. Epub 2003 Jul 24. PubMed PMID: 12881530.

190: Poindessous V, Koeppel F, Raymond E, Comisso M, Waters SJ, Larsen AK. Marked activity of irofulven toward human carcinoma cells: comparison with cisplatin and ecteinascidin. Clin Cancer Res. 2003 Jul;9(7):2817-25. PubMed PMID: 12855662.

191: Bayes M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2003 May;25(4):317-40. PubMed PMID: 12808477.

192: Taguchi T. [Development of marine-derived anti-cancer compounds]. Gan To Kagaku Ryoho. 2003 May;30(5):579-88. Review. Japanese. PubMed PMID: 12795086.

193: Held-Warmkessel J. Ecteinascidin-743. Clin J Oncol Nurs. 2003 May-Jun;7(3):313-9. Review. PubMed PMID: 12793338.

194: Jin W, Metobo S, Williams RM. Synthetic studies on ecteinascidin-743: constructing a versatile pentacyclic intermediate for the synthesis of ecteinascidins and saframycins. Org Lett. 2003 Jun 12;5(12):2095-8. PubMed PMID: 12790537.

195: Meco D, Colombo T, Ubezio P, Zucchetti M, Zaffaroni M, Riccardi A, Faircloth G, Jose J, D'Incalci M, Riccardi R. Effective combination of ET-743 and doxorubicin in sarcoma: preclinical studies. Cancer Chemother Pharmacol. 2003 Aug;52(2):131-8. Epub 2003 May 29. PubMed PMID: 12783202.

196: Bayés M, Rabasseda X, Prous JR. Gateways to clinical trials. March 2003. Methods Find Exp Clin Pharmacol. 2003 Mar;25(2):145-68. PubMed PMID: 12731460.

197: Sainz-Diaz CI, Manzanares I, Francesch A, Garcia-Ruiz J. The potent anticancer compound ecteinascidin-743 (ET-743) as its 2-propanol disolvate. Acta Crystallogr C. 2003 Apr;59(Pt 4):O197-8. Epub 2003 Mar 21. PubMed PMID: 12682407.

198: Lansiaux A, Bailly C. [Perspectives on the oncologist pharmacopoeia]. Bull Cancer. 2003 Jan;90(1):25-30. French. PubMed PMID: 12609801.

199: Biroccio A, Gabellini C, Amodei S, Benassi B, Del Bufalo D, Elli R, Antonelli A, D'Incalci M, Zupi G. Telomere dysfunction increases cisplatin and ecteinascidin-743 sensitivity of melanoma cells. Mol Pharmacol. 2003 Mar;63(3):632-8. PubMed PMID: 12606771.

200: Trabectedin: ET 743, ecteinascidin 743, Yondelis. Drugs R D. 2003;4(1):75-81. Review. PubMed PMID: 12568645.

201: Kanzaki A, Takebayashi Y, Ren XQ, Miyashita H, Mori S, Akiyama S, Pommier Y. Overcoming multidrug drug resistance in P-glycoprotein/MDR1-overexpressing cell lines by ecteinascidin 743. Mol Cancer Ther. 2002 Dec;1(14):1327-34. PubMed PMID: 12516966.

202: Ryan DP, Puchalski T, Supko JG, Harmon D, Maki R, Garcia-Carbonero R, Kuhlman C, Winkelman J, Merriam P, Quigley T, Jimeno J, Manola J, Demetri GD. A phase II and pharmacokinetic study of ecteinascidin 743 in patients with gastrointestinal stromal tumors. Oncologist. 2002;7(6):531-8. PubMed PMID: 12490740.

203: Scotlandi K, Perdichizzi S, Manara MC, Serra M, Benini S, Cerisano V, Strammiello R, Mercuri M, Reverter-Branchat G, Faircloth G, D'Incalci M, Picci P. Effectiveness of Ecteinascidin-743 against drug-sensitive and -resistant bone tumor cells. Clin Cancer Res. 2002 Dec;8(12):3893-903. PubMed PMID: 12473605.

204: Takahashi N, Li W, Banerjee D, Guan Y, Wada-Takahashi Y, Brennan MF, Chou TC, Scotto KW, Bertino JR. Sequence-dependent synergistic cytotoxicity of ecteinascidin-743 and paclitaxel in human breast cancer cell lines in vitro and in vivo. Cancer Res. 2002 Dec 1;62(23):6909-15. PubMed PMID: 12460906.

205: Patel SR. Developing therapeutic pharmaceuticals for the treatment of soft-tissue sarcomas. Expert Opin Investig Drugs. 2002 Dec;11(12):1789-93. Review. PubMed PMID: 12457438.

206: Burton A. Sea squirt assaults sarcomas. Lancet Oncol. 2002 Nov;3(11):648. PubMed PMID: 12424055.

207: Puchalski TA, Ryan DP, Garcia-Carbonero R, Demetri GD, Butkiewicz L, Harmon D, Seiden MV, Maki RG, Lopez-Lazaro L, Jimeno J, Guzman C, Supko JG. Pharmacokinetics of ecteinascidin 743 administered as a 24-h continuous intravenous infusion to adult patients with soft tissue sarcomas: associations with clinical characteristics, pathophysiological variables and toxicity. Cancer Chemother Pharmacol. 2002 Oct;50(4):309-19. Epub 2002 Jul 31. PubMed PMID: 12357306.

208: Reid JM, Kuffel MJ, Ruben SL, Morales JJ, Rinehart KL, Squillace DP, Ames MM. Rat and human liver cytochrome P-450 isoform metabolism of ecteinascidin 743 does not predict gender-dependent toxicity in humans. Clin Cancer Res. 2002 Sep;8(9):2952-62. PubMed PMID: 12231541.

209: Gajate C, An F, Mollinedo F. Differential cytostatic and apoptotic effects of ecteinascidin-743 in cancer cells. Transcription-dependent cell cycle arrest and transcription-independent JNK and mitochondrial mediated apoptosis. J Biol Chem. 2002 Nov 1;277(44):41580-9. Epub 2002 Aug 26. PubMed PMID: 12198119.

210: Demetri GD. ET-743: the US experience in sarcomas of soft tissues. Anticancer Drugs. 2002 May;13 Suppl 1:S7-9. Review. PubMed PMID: 12173492.

211: Scotto KW. ET-743: more than an innovative mechanism of action. Anticancer Drugs. 2002 May;13 Suppl 1:S3-6. Review. PubMed PMID: 12173491.

212: Jimeno JM. A clinical armamentarium of marine-derived anti-cancer compounds. Anticancer Drugs. 2002 May;13 Suppl 1:S15-9. Review. PubMed PMID: 12173490.

213: Brain EG. Safety and efficacy of ET-743: the French experience. Anticancer Drugs. 2002 May;13 Suppl 1:S11-4. Review. PubMed PMID: 12173489.

214: Aune GJ, Furuta T, Pommier Y. Ecteinascidin 743: a novel anticancer drug with a unique mechanism of action. Anticancer Drugs. 2002 Jul;13(6):545-55. Review. PubMed PMID: 12172500.

215: Chabner BA. Cytotoxic agents in the era of molecular targets and genomics. Oncologist. 2002;7 Suppl 3:34-41. Review. PubMed PMID: 12165653.

216: Donald S, Verschoyle RD, Edwards R, Judah DJ, Davies R, Riley J, Dinsdale D, Lopez Lazaro L, Smith AG, Gant TW, Greaves P, Gescher AJ. Hepatobiliary damage and changes in hepatic gene expression caused by the antitumor drug ecteinascidin-743 (ET-743) in the female rat. Cancer Res. 2002 Aug 1;62(15):4256-62. PubMed PMID: 12154027.

217: Albella B, Faircloth G, López-Lázaro L, Guzmán C, Jimeno J, Bueren JA. In vitro toxicity of ET-743 and aplidine, two marine-derived antineoplastics, on human bone marrow haematopoietic progenitors. comparison with the clinical results. Eur J Cancer. 2002 Jul;38(10):1395-404. PubMed PMID: 12091072.

218: D'Incalci M. Editorial comment on "In vitro toxicity of ET-743 and Aplidine, two marine-derived antineoplastics, on human bone marrow haematopoietic progenitors: comparison with the clinical results" by Albella and colleagues. Eur J Cancer. 2002 Jul;38(10):1297. PubMed PMID: 12091058.

219: Friedman D, Hu Z, Kolb EA, Gorfajn B, Scotto KW. Ecteinascidin-743 inhibits activated but not constitutive transcription. Cancer Res. 2002 Jun 15;62(12):3377-81. PubMed PMID: 12067978.

220: D'Incalci M, Erba E, Damia G, Galliera E, Carrassa L, Marchini S, Mantovani R, Tognon G, Fruscio R, Jimeno J, Faircloth GT. Unique features of the mode of action of ET-743. Oncologist. 2002;7(3):210-6. Review. PubMed PMID: 12065793.

221: Endo A, Yanagisawa A, Abe M, Tohma S, Kan T, Fukuyama T. Total synthesis of ecteinascidin 743. J Am Chem Soc. 2002 Jun 12;124(23):6552-4. PubMed PMID: 12047173.

222: Plowright AT, Schaus SE, Myers AG. Transcriptional response pathways in a yeast strain sensitive to saframycin a and a more potent analog: evidence for a common basis of activity. Chem Biol. 2002 May;9(5):607-18. PubMed PMID: 12031667.

223: Cvetkovic RS, Figgitt DP, Plosker GL. ET-743. Drugs. 2002;62(8):1185-92; discussion 1193-4. Review. Erratum in: Drugs 2002;62(11):1634. PubMed PMID: 12010079.

224: van Kesteren C, Twelves C, Bowman A, Hoekman K, López-Lázaro L, Jimeno J, Guzman C, Mathôt RA, Simpson A, Vermorken JB, Smyth J, Schellens JH, Hillebrand MJ, Rosing H, Beijnen JH. Clinical pharmacology of the novel marine-derived anticancer agent Ecteinascidin 743 administered as a 1- and 3-h infusion in a phase I study. Anticancer Drugs. 2002 Apr;13(4):381-93. PubMed PMID: 11984084.

225: Marco E, García-Nieto R, Mendieta J, Manzanares I, Cuevas C, Gago F. A 3.(ET743)-DNA complex that both resembles an RNA-DNA hybrid and mimicks zinc finger-induced DNA structural distortions. J Med Chem. 2002 Feb 14;45(4):871-80. PubMed PMID: 11831898.

226: Villalona-Calero MA, Eckhardt SG, Weiss G, Hidalgo M, Beijnen JH, van Kesteren C, Rosing H, Campbell E, Kraynak M, Lopez-Lazaro L, Guzman C, Von Hoff DD, Jimeno J, Rowinsky EK. A phase I and pharmacokinetic study of ecteinascidin-743 on a daily x 5 schedule in patients with solid malignancies. Clin Cancer Res. 2002 Jan;8(1):75-85. PubMed PMID: 11801542.

227: van Kesteren C, Mathĵt RA, López-Lázaro L, Cvitkovic E, Taamma A, Jimeno JM, Guzman C, Schellens JH, Misset JL, Brain E, Hillebrand MJ, Rosing H, Beijnen JH. A comparison of limited sampling strategies for prediction of Ecteinascidin 743 clearance when administered as a 24-h infusion. Cancer Chemother Pharmacol. 2001 Dec;48(6):459-66. PubMed PMID: 11800026.

228: Zhou B, Guo J, Danishefsky SJ. Studies directed to the total synthesis of ET 743 and analogues thereof: an expeditious route to the ABFGH subunit. Org Lett. 2002 Jan 10;4(1):43-6. PubMed PMID: 11772086.

229: Hurley LH, Zewail-Foote M. The antitumor agent ecteinascidin 743: characterization of its covalent DNA adducts and chemical stability. Adv Exp Med Biol. 2001;500:289-99. Review. PubMed PMID: 11764956.

230: Verschraegen CF, Glover K. ET-743 (PharmaMar/NCI/Ortho Biotech). Curr Opin Investig Drugs. 2001 Nov;2(11):1631-8. Review. PubMed PMID: 11763168.

231: Martinez EJ, Corey EJ, Owa T. Antitumor activity- and gene expression-based profiling of ecteinascidin Et 743 and phthalascidin Pt 650. Chem Biol. 2001 Dec;8(12):1151-60. PubMed PMID: 11755394.

232: Zewail-Foote M, Li VS, Kohn H, Bearss D, Guzman M, Hurley LH. The inefficiency of incisions of ecteinascidin 743-DNA adducts by the UvrABC nuclease and the unique structural feature of the DNA adducts can be used to explain the repair-dependent toxicities of this antitumor agent. Chem Biol. 2001 Nov;8(11):1033-49. Erratum in: Chem Biol. 2004 Feb;11(2):283. PubMed PMID: 11731295.

233: Sparidans RW, Rosing H, Hillebrand MJ, López-Lázaro L, Jimeno JM, Manzanares I, van Kesteren C, Cvitkovic E, van Oosterom AT, Schellens JH, Beijnen JH. Search for metabolites of ecteinascidin 743, a novel, marine-derived, anti-cancer agent, in man. Anticancer Drugs. 2001 Sep;12(8):653-66. PubMed PMID: 11604552.

234: Ray-Coquard I, Biron P, Blay JY. [High-dose chemotherapy in soft tissue sarcomas of adults]. Bull Cancer. 2001 Sep;88(9):858-62. Review. French. PubMed PMID: 11604358.

235: Takahashi N, Li WW, Banerjee D, Scotto KW, Bertino JR. Sequence-dependent enhancement of cytotoxicity produced by ecteinascidin 743 (ET-743) with doxorubicin or paclitaxel in soft tissue sarcoma cells. Clin Cancer Res. 2001 Oct;7(10):3251-7. PubMed PMID: 11595721.

236: Li WW, Takahashi N, Jhanwar S, Cordon-Cardo C, Elisseyeff Y, Jimeno J, Faircloth G, Bertino JR. Sensitivity of soft tissue sarcoma cell lines to chemotherapeutic agents: identification of ecteinascidin-743 as a potent cytotoxic agent. Clin Cancer Res. 2001 Sep;7(9):2908-11. PubMed PMID: 11555609.

237: Takebayashi Y, Pourquier P, Zimonjic DB, Nakayama K, Emmert S, Ueda T, Urasaki Y, Kanzaki A, Akiyama SI, Popescu N, Kraemer KH, Pommier Y. Antiproliferative activity of ecteinascidin 743 is dependent upon transcription-coupled nucleotide-excision repair. Nat Med. 2001 Aug;7(8):961-6. Erratum in: Nat Med 2001 Nov;7(11):1255. PubMed PMID: 11479630.

238: Bonetta L. Anticancer squirt. Nat Med. 2001 Aug;7(8):891. PubMed PMID: 11479616.

239: Zewail-Foote M, Hurley LH. Differential rates of reversibility of ecteinascidin 743-DNA covalent adducts from different sequences lead to migration to favored bonding sites. J Am Chem Soc. 2001 Jul 11;123(27):6485-95. PubMed PMID: 11439034.

240: Adams J, Elliott PJ. New agents in cancer clinical trials. Oncogene. 2000 Dec 27;19(56):6687-92. Review. PubMed PMID: 11426656.

241: Synold TW, Dussault I, Forman BM. The orphan nuclear receptor SXR coordinately regulates drug metabolism and efflux. Nat Med. 2001 May;7(5):584-90. PubMed PMID: 11329060.

242: Finch JS, Rosenberger SF, Martinez JD, Bowden GT. Okadaic acid induces transcription of junB through a CCAAT box and NF-Y. Gene. 2001 Apr 4;267(1):135-44. PubMed PMID: 11311563.

243: Damia G, Silvestri S, Carrassa L, Filiberti L, Faircloth GT, Liberi G, Foiani M, D'Incalci M. Unique pattern of ET-743 activity in different cellular systems with defined deficiencies in DNA-repair pathways. Int J Cancer. 2001 May 15;92(4):583-8. PubMed PMID: 11304695.

244: Ryan DP, Supko JG, Eder JP, Seiden MV, Demetri G, Lynch TJ, Fischman AJ, Davis J, Jimeno J, Clark JW. Phase I and pharmacokinetic study of ecteinascidin 743 administered as a 72-hour continuous intravenous infusion in patients with solid malignancies. Clin Cancer Res. 2001 Feb;7(2):231-42. PubMed PMID: 11234874.

245: Taamma A, Misset JL, Riofrio M, Guzman C, Brain E, Lopez Lazaro L, Rosing H, Jimeno JM, Cvitkovic E. Phase I and pharmacokinetic study of ecteinascidin-743, a new marine compound, administered as a 24-hour continuous infusion in patients with solid tumors. J Clin Oncol. 2001 Mar 1;19(5):1256-65. PubMed PMID: 11230466.

246: Delaloge S, Yovine A, Taamma A, Riofrio M, Brain E, Raymond E, Cottu P, Goldwasser F, Jimeno J, Misset JL, Marty M, Cvitkovic E. Ecteinascidin-743: a marine-derived compound in advanced, pretreated sarcoma patients--preliminary evidence of activity. J Clin Oncol. 2001 Mar 1;19(5):1248-55. PubMed PMID: 11230465.

247: Takebayashi Y, Goldwasser F, Urasaki Y, Kohlhagen G, Pommier Y. Ecteinascidin 743 induces protein-linked DNA breaks in human colon carcinoma HCT116 cells and is cytotoxic independently of topoisomerase I expression. Clin Cancer Res. 2001 Jan;7(1):185-91. PubMed PMID: 11205907.

248: Erba E, Bergamaschi D, Bassano L, Damia G, Ronzoni S, Faircloth GT, D'Incalci M. Ecteinascidin-743 (ET-743), a natural marine compound, with a unique mechanism of action. Eur J Cancer. 2001 Jan;37(1):97-105. PubMed PMID: 11165136.

249: Smyth JF. Science and serendipity in cancer research. Eur J Cancer. 2001 Jan;37(1):8. PubMed PMID: 11165123.

250: van Kesteren C, Cvitkovic E, Taamma A, López-Lázaro L, Jimeno JM, Guzman C, Math t RA, Schellens JH, Misset JL, Brain E, Hillebrand MJ, Rosing H, Beijnen JH. Pharmacokinetics and pharmacodynamics of the novel marine-derived anticancer agent ecteinascidin 743 in a phase I dose-finding study. Clin Cancer Res. 2000 Dec;6(12):4725-32. PubMed PMID: 11156226.

251: García-Nieto R, Manzanares I, Cuevas C, Gago F. Increased DNA binding specificity for antitumor ecteinascidin 743 through protein-DNA interactions? J Med Chem. 2000 Nov 16;43(23):4367-9. PubMed PMID: 11087561.

252: Saito N, Tachi M, Seki R, Kamayachi H, Kubo A. A practical synthesis of the ABC ring model of ecteinascidins. Chem Pharm Bull (Tokyo). 2000 Oct;48(10):1549-57. PubMed PMID: 11045468.

253: Cuevas C, Pérez M, Martín MJ, Chicharro JL, Fernández-Rivas C, Flores M, Francesch A, Gallego P, Zarzuelo M, de La Calle F, García J, Polanco C, Rodríguez I, Manzanares I. Synthesis of ecteinascidin ET-743 and phthalascidin Pt-650 from cyanosafracin B. Org Lett. 2000 Aug 10;2(16):2545-8. PubMed PMID: 10956543.

254: Minuzzo M, Marchini S, Broggini M, Faircloth G, D'Incalci M, Mantovani R. Interference of transcriptional activation by the antineoplastic drug ecteinascidin-743. Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6780-4. PubMed PMID: 10841573; PubMed Central PMCID: PMC18737.

255: Jin S, Gorfajn B, Faircloth G, Scotto KW. Ecteinascidin 743, a transcription-targeted chemotherapeutic that inhibits MDR1 activation. Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6775-9. PubMed PMID: 10841572; PubMed Central PMCID: PMC18735.

256: Martinez EJ, Corey EJ. Enantioselective synthesis of saframycin A and evaluation of antitumor activity relative to ecteinascidin/saframycin hybrids. Org Lett. 1999 Jul 15;1(1):75-7. PubMed PMID: 10822537.

257: Erba E, Bergamaschi D, Bassano L, Ronzoni S, Di Liberti G, Muradore I, Vignati S, Faircloth G, Jimeno J, D'Incalci M. Isolation and characterization of an IGROV-1 human ovarian cancer cell line made resistant to Ecteinascidin-743 (ET-743). Br J Cancer. 2000 May;82(10):1732-9. PubMed PMID: 10817511; PubMed Central PMCID: PMC2374505.

258: Martinez EJ, Corey EJ. A new, more efficient, and effective process for the synthesis of a key pentacyclic intermediate for production of ecteinascidin and phthalascidin antitumor agents. Org Lett. 2000 Apr 6;2(7):993-6. PubMed PMID: 10768205.

259: Hendriks HR, Fiebig HH, Giavazzi R, Langdon SP, Jimeno JM, Faircloth GT. High antitumour activity of ET743 against human tumour xenografts from melanoma, non-small-cell lung and ovarian cancer. Ann Oncol. 1999 Oct;10(10):1233-40. PubMed PMID: 10586342.

260: Bonfanti M, La Valle E, Fernandez Sousa Faro JM, Faircloth G, Caretti G, Mantovani R, D'Incalci M. Effect of ecteinascidin-743 on the interaction between DNA binding proteins and DNA. Anticancer Drug Des. 1999 Jun;14(3):179-86. PubMed PMID: 10500494.

261: Zewail-Foote M, Hurley LH. Ecteinascidin 743: a minor groove alkylator that bends DNA toward the major groove. J Med Chem. 1999 Jul 15;42(14):2493-7. PubMed PMID: 10411470.

262: Takebayashi Y, Pourquier P, Yoshida A, Kohlhagen G, Pommier Y. Poisoning of human DNA topoisomerase I by ecteinascidin 743, an anticancer drug that selectively alkylates DNA in the minor groove. Proc Natl Acad Sci U S A. 1999 Jun 22;96(13):7196-201. PubMed PMID: 10377391; PubMed Central PMCID: PMC22050.

263: Martinez EJ, Owa T, Schreiber SL, Corey EJ. Phthalascidin, a synthetic antitumor agent with potency and mode of action comparable to ecteinascidin 743. Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3496-501. PubMed PMID: 10097064; PubMed Central PMCID: PMC22321.

264: Lansiaux A, Bailly C. [Ecteinascidin 743]. Bull Cancer. 1999 Feb;86(2):139-41. Review. French. PubMed PMID: 10094523.

265: Rosing H, Hillebrand MJ, Jimeno JM, Gómez A, Floriano P, Faircloth G, Henrar RE, Vermorken JB, Cvitkovic E, Bult A, Beijnen JH. Quantitative determination of Ecteinascidin 743 in human plasma by miniaturized high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry. J Mass Spectrom. 1998 Nov;33(11):1134-40. PubMed PMID: 9835068.

266: Ghielmini M, Colli E, Erba E, Bergamaschi D, Pampallona S, Jimeno J, Faircloth G, Sessa C. In vitro schedule-dependency of myelotoxicity and cytotoxicity of Ecteinascidin 743 (ET-743). Ann Oncol. 1998 Sep;9(9):989-93. PubMed PMID: 9818073.

267: Izbicka E, Lawrence R, Raymond E, Eckhardt G, Faircloth G, Jimeno J, Clark G, Von Hoff DD. In vitro antitumor activity of the novel marine agent, ecteinascidin-743 (ET-743, NSC-648766) against human tumors explanted from patients. Ann Oncol. 1998 Sep;9(9):981-7. PubMed PMID: 9818072.

268: D'Incalci M. Some hope from marine natural products. Ann Oncol. 1998 Sep;9(9):937-8. PubMed PMID: 9818065.

269: Valoti G, Nicoletti MI, Pellegrino A, Jimeno J, Hendriks H, D'Incalci M, Faircloth G, Giavazzi R. Ecteinascidin-743, a new marine natural product with potent antitumor activity on human ovarian carcinoma xenografts. Clin Cancer Res. 1998 Aug;4(8):1977-83. PubMed PMID: 9717828.

270: Rosing H, Hillebrand MJ, Jimeno JM, Gómez A, Floriano P, Faircloth G, Cameron L, Henrar RE, Vermorken JB, Bult A, Beijnen JH. Analysis of Ecteinascidin 743, a new potent marine-derived anticancer drug, in human plasma by high-performance liquid chromatography in combination with solid-phase extraction. J Chromatogr B Biomed Sci Appl. 1998 Jun 12;710(1-2):183-9. PubMed PMID: 9686886.

271: Pommier Y, Kohlhagen G, Bailly C, Waring M, Mazumder A, Kohn KW. DNA sequence- and structure-selective alkylation of guanine N2 in the DNA minor groove by ecteinascidin 743, a potent antitumor compound from the Caribbean tunicate Ecteinascidia turbinata. Biochemistry. 1996 Oct 15;35(41):13303-9. PubMed PMID: 8873596.

272: García-Rocha M, García-Gravalos MD, Avila J. Characterisation of antimitotic products from marine organisms that disorganise the microtubule network: ecteinascidin 743, isohomohalichondrin-B and LL-15. Br J Cancer. 1996 Apr;73(8):875-83. PubMed PMID: 8611420; PubMed Central PMCID: PMC2075815.