High-throughput screening identifies Aurora kinase B as a critical therapeutic target for Merkel cell carcinoma.

ABSTRACT: Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer. Most MCCs contain Merkel cell polyomavirus (virus-positive MCC; VP-MCC), and the remaining are virus-negative (VN-MCC). Immune checkpoint inhibitors are the first-line treatment for metastatic MCC, but durable responses are achieved in less than 50% of patients. To identify new treatments, we screen ~4,000 compounds for their ability to reduce MCC viability and demonstrate that VP-MCC and VN-MCC exhibit distinct response profiles. Aurora kinase inhibitors selectively reduce VP-MCC viability, with RNAi screening independently identifying AURKB as an essential gene for MCC survival, especially in VP-MCC. AZD2811, a selective AURKB inhibitor, induces mitotic dysregulation and apoptosis in MCC cells, with greater efficacy in VP-MCC

SUBMITTER: Gelb T 

PROVIDER: S-EPMC11822212 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature