pomalidomide + verteporfin

Pomalidomide + verteporfin is an experimental combination therapy primarily investigated for the treatment of relapsed or refractory multiple myeloma. Pomalidomide is a third-generation immunomodulatory imide drug (IMiD) that functions by binding to cereblon (CRBN), a component of the CRL4-CRBN E3 ubiquitin ligase complex. This binding triggers the selective ubiquitination and subsequent proteasomal degradation of the lymphoid transcription factors Ikaros (IKZF1) and Aiolos (IKZF3), leading to the inhibition of myeloma cell growth and the stimulation of T-cell and natural killer cell activity. Verteporfin, a benzoporphyrin derivative traditionally used as a photosensitizer in photodynamic therapy for macular degeneration, has been repurposed in oncology as a small molecule inhibitor of the Hippo pathway effector YAP1 (Yes-associated protein 1). In multiple myeloma, YAP1 has been identified as a critical survival factor that is often upregulated in response to DNA damage and contributes to IMiD resistance. The combination of pomalidomide and verteporfin is designed to synergistically induce apoptosis by simultaneously degrading Ikaros/Aiolos and inhibiting YAP1-mediated survival signaling, thereby potentially overcoming resistance to standard-of-care immunomodulatory therapies.

Other names

pomalidomide and verteporfin