2. Academic Validation
  3. CDK4/6 Inhibition in Cancer: Beyond Cell Cycle Arrest

CDK4/6 Inhibition in Cancer: Beyond Cell Cycle Arrest

  • Trends Cell Biol. 2018 Nov;28(11):911-925. doi: 10.1016/j.tcb.2018.07.002.
Shom Goel 1,  Molly J DeCristo 2,  Sandra S McAllister 3,  Jean J Zhao 4
Affiliations

Affiliations

  • 1 Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. Electronic address: shom_goel@dfci.harvard.edu.
  • 2 Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • 3 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.
  • 4 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: jean_zhao@dfci.harvard.edu.
PMID: 30061045 DOI: 10.1016/j.tcb.2018.07.002
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.

Keywords

CDK4/6; cell cycle; immunotherapy; targeted therapy.

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