guadecitabine + carboplatin

Guadecitabine + carboplatin is a combination regimen consisting of guadecitabine, a next-generation hypomethylating agent (HMA), and carboplatin, a platinum-based chemotherapy. Guadecitabine is a dinucleotide prodrug of decitabine administered subcutaneously, leading to prolonged exposure and enhanced DNA hypomethylation compared to earlier HMAs. Its mechanism involves inhibition of DNA methyltransferase, leading to DNA hypomethylation and the re-expression of silenced tumor suppressor genes, potentially restoring chemosensitivity. Carboplatin induces DNA crosslinking and damage, leading to apoptosis. The combination was investigated primarily for resensitizing platinum-resistant (high-grade) serous ovarian cancer, including primary peritoneal carcinoma and fallopian tube cancer. The regimen aims to overcome platinum resistance, induce apoptosis in tumor cells, and promote anti-tumor responses by priming the tumor epigenetically before carboplatin exposure.