Examining the In Vitro Efficacy of the IAP Antagonist Birinapant as a Single Agent or in Combination With Dacarbazine to Induce Melanoma Cell Death

• DOI: 10.3727/096504017x14897145996933
• Publication Date: 2017-03-24T11:05:59Z
• Authors: Vesna Vetma; Jan Rožanc; Emilie M. Charles; Christian T. Hellwig; Leonidas G. Alexo...; Markus Rehm
• Keywords: Dacarbazine; Temozolomide; Ex vivo

Antagonists of inhibitors apoptosis proteins (IAPs), alone or in combination with genotoxic therapeutics, have been shown to efficiently induce cell death various solid tumors. The IAP antagonist birinapant is currently being tested phase II clinical trials. We herein aimed investigate the antitumor efficacy dacarbazine vitro, both as a single agent and birinapant, melanoma lines. Covering clinically relevant drug concentration ranges, we conducted total 5,400 measurements panel 12 human lines representing different stages disease progression. Surprisingly, functionally synergies response potentiation treatments was not observed, only one line modestly responded treatment (approximately 16% death). Although did study underlying resistance mechanisms more complex vivo scenarios which dacarbazine/birinapant may still possibly manifest, our findings are nevertheless noteworthy because antagonists were demonstrated strongly enhance responses DNA-damaging agents other cancer types under comparable experimental conditions vitro.