TY - JOUR
T1 - Chemotherapy and CDK4/6 inhibitors
T2 - Unexpected bedfellows
AU - Roberts, Patrick J.
AU - Kumarasamy, Vishnu
AU - Witkiewicz, Agnieszka K.
AU - Knudsen, Erik S.
N1 - Funding Information:
The authors acknowledge their colleagues at Roswell Park and G1 Therapeutics for thoughtful discussion and review of the manuscript. This work was supported by grants AKW and ESK from the NIH CA211878 and CA247362.
Publisher Copyright:
© 2020 American Association for Cancer Research.
PY - 2020/8/1
Y1 - 2020/8/1
N2 - 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.
AB - 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.
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U2 - 10.1158/1535-7163.MCT-18-1161
DO - 10.1158/1535-7163.MCT-18-1161
M3 - Review article
C2 - 32546660
AN - SCOPUS:85089163555
VL - 19
SP - 1575
EP - 1588
JO - Molecular Cancer Therapeutics
JF - Molecular Cancer Therapeutics
SN - 1535-7163
IS - 8
ER -