pralatrexate + bexarotene

**pralatrexate + bexarotene** is a fixed-dose combination of two **small molecule antineoplastic agents** developed and studied for the treatment of **relapsed or refractory cutaneous T-cell lymphoma (CTCL)**, including its major variants mycosis fungoides and Sézary syndrome. **Pralatrexate** is a rationally designed antifolate that competitively inhibits dihydrofolate reductase (DHFR), disrupting DNA synthesis and repair, leading to apoptosis in rapidly proliferating cells. **Bexarotene** is a synthetic retinoid that selectively activates retinoid X receptors (RXRs), affecting gene transcription and promoting cellular differentiation and apoptosis. The combination demonstrates synergistic antitumor effects, with improved overall response rates compared to either drug alone, and is especially notable for durable responses in patients with advanced or refractory disease. Developed and trialed in the U.S., the combination has not received regulatory approval as a fixed combination product but has reached Phase II clinical trials for CTCL.