A novel CDK12 inhibitor induces homologous recombination deficiency to enhance PARP inhibitor efficacy in uterine serous carcinoma - PubMed
7 hours ago
- #uterine serous carcinoma
- #CDK12 inhibitor
- #PARP inhibitor
- A novel CDK12 inhibitor, CTX-439, enhances PARP inhibitor efficacy in uterine serous carcinoma (USC).
- USC has higher homologous recombination deficiency (HRD) scores than other uterine endometrial carcinoma subtypes but lower than high-grade serous ovarian carcinoma (HGSOC).
- CDK12 amplification is more frequent in USC than HGSOC, correlating with poor prognosis but not HRD scores.
- CTX-439 suppresses HR-related genes (e.g., BRCA1, BRCA2), induces apoptosis, DNA damage, and inhibits tumor growth in USC models.
- Combining CDK12 inhibition with PARP inhibitor olaparib enhances tumor sensitivity in USC patient-derived xenograft (PDX) models.
- CDK12 is a potential therapeutic target to improve PARP inhibitor efficacy in USC patients.