Emerging roles of bexarotene in the prevention, treatment and anti-drug resistance of cancers

ABSTRACT

Introduction: Retinoic acid X receptors play key roles in tumor cell proliferation, differentiation, apoptosis and angiogenesis via transcriptional regulation. Bexarotene is a specific RXRs agonist which has been granted by FDA approval for the clinical treatment of cutaneous T cell lymphoma (CTCL). Its cancer prevention and treatment potentials in various tumors have been under investigation over the past decade.

Areas covered: This review summarizes the efficacy and underlying mechanisms of bexarotene for the treatment of multiple cancers based on the launched clinical trials as well as the basic studies.

Expert commentary: In general, bexarotene is an active and reasonable chemoprevention and treatment for various cancers and its combination regimen with other cytotoxic agents or targeted drugs may significantly enhance efficacy and at the same time reduce toxicity due to their nonoverlapping side effects. However, only a subpopulation of bexarotene treated patients benefited from bexarotene administration in most cases. The level of RXRs may serve as a preliminary indicator for the bexarotene response in cancers such as non-small cell lung cancer, acute myeloid leukemia, breast cancer, thyroid cancer and melanoma. Further identification and verification of bexarotene response biomarkers may finally lead to the personalized clinical application of bexarotene on cancers beyond CTCL.

KEYWORDS:

• Bexarotene
• cancer prevention
• cancer treatment
• drug resistance
• drug response

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript has received funding from the National Natural Science Foundation of China (Grant Numbers: 81773789, 21402173, 81672520); Zhejiang Provincial Natural Science Foundation of China (grant numbers: LY17H160020, LY17H050003); Zhejiang province medical program (2014ZDA011, 2014KYB134).