M4344 + carboplatin

M4344 (gartisertib, VX-803) plus carboplatin is an investigational combination therapy explored for advanced solid tumors. **M4344 is an oral, highly potent and selective inhibitor of ATR (axia telangiectasia and Rad3-related protein kinase),** a master regulator of the DNA damage response (DDR) pathway. By inhibiting ATR, M4344 impairs cancer cells' ability to repair replication stress and DNA damage, thereby inducing replication catastrophe and increasing susceptibility to DNA-damaging agents. **Carboplatin** is a well-established platinum-based chemotherapy that induces DNA crosslinks and cytotoxicity. The combination aims to enhance the efficacy of standard chemotherapy by heightening replication stress and DNA damage in tumor cells, particularly those reliant on ATR for survival or with defective DNA repair mechanisms. Early-phase clinical trials have focused on determining the safety, tolerability, and maximum tolerated dose of the combination in patients with advanced solid tumors, with evidence of strong synergy observed in preclinical models and rationale for targeting chemoresistant cancers[1][2][3][4][5].

Other names

gartisertib + carboplatin