Targeting CDK2 Confers Vulnerability to Lenvatinib Via Driving Senescence in Anaplastic Thyroid Cancer.

ABSTRACT: Anaplastic thyroid cancer (ATC) is the most lethal tumor arising from thyroid follicular epithelium. Lenvatinib is an off-label use option for ATC patients in many countries but an approved prescription in Japan. However, lenvatinib resistance is a substantial clinical challenge. Clinical ATC samples including lenvatinib-resistant tumors are used to build patient-derived cells and patient-derived xenografts. High-throughput drug screening and synergy analyses are performed to identify an effective combination partner for lenvatinib. Cellular functions are detected by cell senescence, apoptosis, cell cycle, cell viability and colony formation assays. CDK2 inhibition showed the significant synthetic lethality with lenvatinib via inhibiting G1/S transition and inducing cell senescence in ATC.

SUBMITTER: Ma B 

PROVIDER: S-EPMC11831524 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature