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 Bexarotene

Bexarotene is a synthetic retinoic acid agent with potential antineoplastic, chemopreventive, teratogenic and embryotoxic properties. Bexarotene selectively binds to and activates retinoid X receptors (RXRs), thereby inducing changes in gene expression that lead to cell differentiation, decreased cell proliferation, apoptosis of some cancer cell types, and tumor regression. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus).

Bexarotene (Targretin) is an oral antineoplastic agent indicated by the FDA (in 2000) for cutaneous T cell lymphoma. It has been used off-label for lung cancer,  breast cancer, and Kaposi's sarcoma. Bexarotene is indicated for the treatment of cutaneous manifestations of cutaneous T-cell lymphoma in patients who are refractory to at least one prior systemic therapy (oral) and for the topical treatment of cutaneous lesions in patients with CTCL (Stage IA and IB) who have refractory or persistent disease after other therapies or who have not tolerated other therapies (topical).

Bexarotene is an off-white to white powder with a molecular weight of 348.48 and a molecular formula of C24H28O2. It is insoluble in water and slightly soluble in vegetable oils and ethanol, USP. Each Targretin® (bexarotene) capsule also contains the following inactive ingredients: polyethylene glycol 400, NF, polysorbate 20, NF, povidone, USP, and butylated hydroxyanisole, NF. The capsule shell contains gelatin, NF, sorbitol special-glycerin blend, and titanium dioxide, USP.

Mechanism of Action:
Bexarotene selectively binds and activates retinoid X receptor subtypes (RXRα, RXRβ, RXRγ). RXRs can form heterodimers with various receptor partners such as retinoic acid receptors (RARs), vitamin D receptor, thyroid receptor, and peroxisome proliferator activator receptors (PPARs). Once activated, these receptors function as transcription factors that regulate the expression of genes that control cellular differentiation and proliferation. Bexarotene inhibits the growth in vitro of some tumor cell lines of hematopoietic and squamous cell origin. It also induces tumor regression in vivo in some animal models. The exact mechanism of action of bexarotene in the treatment of cutaneous T-cell lymphoma (CTCL) is unknown.

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57: Lin JH, Kim EJ, Bansal A, Seykora J, Richardson SK, Cha XY, Zafar S, Nasta S, Wysocka M, Benoit B, Rook AH, Fakharzadeh SS. Clinical and in vitro resistance to bexarotene in adult T-cell leukemia: loss of RXR-alpha receptor. Blood. 2008 Sep 15;112(6):2484-8. Epub 2008 Jun 16. PubMed PMID: 18559673; PubMed Central PMCID: PMC2532815.

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86: Liu YY, Stokkel MP, Morreau HA, Pereira AM, Romijn JA, Smit JW. Radioiodine therapy after pretreatment with bexarotene for metastases of differentiated thyroid carcinoma. Clin Endocrinol (Oxf). 2008 Apr;68(4):605-9. Epub 2007 Nov 6. PubMed PMID: 17986279.

87: Lokitz ML, Wong HK. Bexarotene and narrowband ultraviolet B phototherapy combination treatment for mycosis fungoides. Photodermatol Photoimmunol Photomed. 2007 Dec;23(6):255-7. PubMed PMID: 17986063.

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