CDK4/6 Inhibition in Cancer: Beyond Cell Cycle Arrest.

Shom Goel, Molly J DeCristo, Sandra S McAllister, Jean J Zhao

Journal: Trends in cell biology 2019;28(11):911-925

PMID: 30061045

Free Full Text on PubMed Central View on PubMed

Abstract

Pharmacologic inhibitors of cyclin-dependent kinases 4 and 6 (CDK4/6) have recently entered the therapeutic armamentarium of clinical oncologists, and show promising activity in patients with breast and other cancers. Although their chief mechanism of action is inhibition of retinoblastoma (RB) protein phosphorylation and thus the induction of cell cycle arrest, CDK4/6 inhibitors alter cancer cell biology in other ways that can also be leveraged for therapeutic benefit. These include modulation of mitogenic kinase signaling, induction of a senescence-like phenotype, and enhancement of cancer cell immunogenicity. We describe here the less-appreciated effects of CDK4/6 inhibitors on cancer cells, and suggest ways by which they might be exploited to enhance the benefits of these agents for cancer patients.

Address: Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. Electronic address: [email protected].; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.; Department of Medicine, Harvard Medical School, Boston, MA, USA; Hematology Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA; Harvard Stem Cell Institute, Harvard Medical School, Boston, MA, USA; Broad Institute of Harvard and MIT, Cambridge, MA, USA.; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA. Electronic address: [email protected].

DOI: 10.1016/j.tcb.2018.07.002

Link outs

Free resources

Full Text Sources:

Other Literature Sources:

Subscription / membership required

Full Text Sources:

MeSH Terms: Cell Cycle Checkpoints, Cyclin-Dependent Kinase 4, Cyclin-Dependent Kinase 6, Humans, Neoplasms, Protein Kinase Inhibitors