prexasertib + cisplatin

**Prexasertib + cisplatin** is a combination of a selective checkpoint kinase 1 (CHK1) inhibitor (prexasertib) and a platinum-based DNA-damaging chemotherapy agent (cisplatin), studied experimentally in advanced and metastatic cancers, including head and neck squamous cell carcinoma and osteosarcoma. Prexasertib acts by inhibiting CHK1 (and at higher concentrations, CHK2), disrupting the DNA damage response and cell cycle checkpoints, thereby increasing cancer cell susceptibility to DNA-damaging agents. Cisplatin intercalates with DNA, causing cross-linking and apoptosis. The rationale for the combination is that CHK1 inhibition impairs tumor cell recovery and repair from cisplatin-induced DNA damage, resulting in synergistic cytotoxicity. This combination has demonstrated antitumor activity and manageable toxicity in early clinical trials, particularly characterized by hematologic adverse events and reversible bone marrow suppression[1][3][4].