Palbociclib Renders Human Papilloma Virus-Negative Head and Neck Squamous Cell Carcinoma Vulnerable to the Senolytic Agent Navitoclax.

ABSTRACT: We demonstrate that inhibition of cyclin-dependent kinases 4/6 (CDK4/6) leads to senescence in human papillomavirus (HPV)-negative (-) head and neck squamous cell carcinoma (HNSCC), but not in HPV-positive (+) HNSCC. The BCL-2 family inhibitor, navitoclax, has been shown to eliminate senescent cells effectively. We evaluated the efficacy of combining palbociclib and navitoclax in HPV^- HNSCC. Three HPV^- HNSCC cell lines (CAL27, HN31, and PCI15B) and three HPV⁺ HNSCC cell lines (UPCI-SCC-090, UPCI-SCC-154, and UM-SCC-47) were treated with palbociclib. Treatment drove reduced expression of phosphorylated Rb (p-Rb) and phenotypic evidence of senescence in all HPV^- cell lines, whereas HPV⁺ cell lines did not display a consistent response by

SUBMITTER: Gadsden NJ 

PROVIDER: S-EPMC8314015 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature