ATR is essential to protect genome integrity during DNA replication in cancer cells. In this first disclosure, Roulston and colleagues identify RP-3500 (NCT04497116), a highly potent and selective oral ATR inhibitor with efficacy as a monotherap. and in combination with PARP inhibitors in several xenograft models. Preclinically, intermittent dosing of RP-3500 maintains efficacy without inducing anemia, a dose-limiting toxicity observed clinically for ATR inhibitors. Furthermore, concurrent administration of RP-3500 with PARP inhibitors on an intermittent schedule provides greater efficacy and reduced toxicity compared to sequential administration, providing an opportunity to maximize clinical benefit for this class of anti-cancer agent.
Hampton and colleagues describe an approach for precision medicine of platinums in the treatment of triple-negative breast cancer (TNBC) through exploitation of the glycosaminoglycan (sGAG) expression of the tumor. The in vivo accumulation and antitumor efficacy of the paradigmatic polynuclear platinum complex Triplatin (BBR3464) in TNBC cells positively correlated with sGAG...