Chemotherapy and CDK4/6 Inhibitors: Unexpected Bedfellows.

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.

journal_name

Mol Cancer Ther

authors

Roberts PJ,Kumarasamy V,Witkiewicz AK,Knudsen ES

doi

10.1158/1535-7163.MCT-18-1161

subject

Has Abstract

pub_date

2020-08-01 00:00:00

pages

1575-1588

issue

8

eissn

1535-7163

issn

1538-8514

pii

1535-7163.MCT-18-1161

journal_volume

19

pub_type

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