Synthetic lethality of cyclin-dependent kinase inhibitor Dinaciclib with VHL-deficiency allows for selective targeting of clear cell renal cell carcinoma.

ABSTRACT: Clear cell renal cell carcinoma (CC-RCC) remains one of the most deadly forms of kidney cancer despite recent advancements in targeted therapeutics, including tyrosine kinase and immune checkpoint inhibitors. Unfortunately, these therapies have not been able to show better than a 16% complete response rate. In this study we evaluated a cyclin-dependent kinase inhibitor, Dinaciclib, as a potential new targeted therapeutic for CC-RCC. In vitro, Dinaciclib showed anti-proliferative and pro-apoptotic effects on CC-RCC cell lines in Cell Titer Glo, Crystal Violet, FACS-based cell cycle analysis, and TUNEL assays. Additionally, these responses were accompanied by a reduction in phospho-Rb and pro-survival MCL-1 cell signaling responses, as well as the induction of caspase 3 and PARP cleav

SUBMITTER: Nelson LJ 

PROVIDER: S-EPMC9037521 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature