Do CDK4/6 inhibitors have potential as targeted therapeutics for squamous cell cancers?. (1st February 2017)

• Record Type: Journal Article
• Authors: Kalu, Nene N.; Johnson, Faye M.
• Is Part Of: Expert opinion on investigational drugs. Volume 26:Number 2(2017)
• Page Start: 207
• Page End: 217
• Publication Date: 2017-02-01
• Subjects: CDK4 -- CDK6 -- squamous cell carcinoma -- lung cancer -- head and neck cancer -- cervical cancer -- anogenital cancers -- CDK4/6 inhibitors; Drugs -- Design -- Periodicals; Drugs, Investigational -- Bibliography; Drugs, Investigational -- Periodicals; 615.1
• DOI: 10.1080/13543784.2017.1274731
• Languages: English
• ISSNs: 1354-3784

Abstract

ABSTRACT: Introduction Dysregulation of cell cycle progression has an established link to neoplasia and cancer progression. Components of the cyclin D-CDK4/6-INK4-Rb pathway are frequently altered in squamous cell carcinomas (SCCs) by diverse mechanisms, including viral oncogene–induced degradation, mutation, deletion, and amplification. Activation of the CDK4/6 pathway may predict response to CDK4/6 inhibitors and provide clinical biomarkers. Recently, the CDK4/6 inhibitor palbociclib showed clinical efficacy in combination with cetuximab in HNSCC patients. Areas covered This review focuses on the current research on the use of CDK4/6 inhibitors, comprising preclinical animal studies through phase II clinical trials across all SCCs. Expert opinion CDK4/6 inhibitors have a proven clinical benefit in breast cancer, but data on SCCs are sparse. Although frequent dysregulation of the cyclin D-CDK4/6-INK4-Rb pathway in SCCs suggests that targeting CDK4/6 may hold promise for improved clinical outcomes, single-agent activity has been modest in preclinical studies and absent in clinical studies. Combinations with immunotherapy or inhibitors of the PI3 K/mTOR or EGFR pathway may be effective. Given that SCCs caused by human papillomavirus have high levels of p16 and low levels of Rb, the CDK4/6 inhibitors are predicted to be ineffective in these cancers.