Chemotherapy and CDK4/6 Inhibitors: Unexpected Bedfellows

Patrick J. Roberts, Vishnu Kumarasamy, Agnieszka K. Witkiewicz, Erik Knudsen

Research output: Contribution to journalReview article

Abstract

Cyclin-dependent kinases 4 and 6 (CDK4/6) have emerged as important therapeutic targets. Pharmacologic inhibitors of these kinases function to inhibit cell-cycle progression and exert other important effects on the tumor and host environment. Because of their impact on the cell cycle, CDK4/6 inhibitors (CDK4/6i) have been hypothesized to antagonize the antitumor effects of cytotoxic chemotherapy in tumors that are CDK4/6 dependent. However, there are multiple preclinical studies that illustrate potent cooperation between CDK4/6i and chemotherapy. Furthermore, the combination of CDK4/6i and chemotherapy is being tested in clinical trials to both enhance antitumor efficacy and limit toxicity. Exploitation of the noncanonical effects of CDK4/6i could also provide an impetus for future studies in combination with chemotherapy. Thus, while seemingly mutually exclusive mechanisms are at play, the combination of CDK4/6 inhibition and chemotherapy could exemplify rational medicine.

Original languageEnglish (US)
Pages (from-to)1575-1588
Number of pages14
JournalMolecular Cancer Therapeutics
Volume19
Issue number8
DOIs
StatePublished - Aug 1 2020
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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