Cyclin-dependent kinases-based synthetic lethality: Evidence, concept, and strategy

Kailin Li; Jieqiong You; Qian Wu; Wen Meng; Qiaojun He; Bo Yang; Chengliang Zhu; Ji Cao

doi:10.1016/j.apsb.2021.01.002

Cyclin-dependent kinases-based synthetic lethality: Evidence, concept, and strategy

Acta Pharm Sin B. 2021 Sep;11(9):2738-2748. doi: 10.1016/j.apsb.2021.01.002. Epub 2021 Jan 7.

Authors

Kailin Li¹, Jieqiong You¹, Qian Wu¹, Wen Meng², Qiaojun He^{1

3

4}, Bo Yang^{1

3}, Chengliang Zhu¹, Ji Cao^{1

3

4}

Affiliations

¹ Institute of Pharmacology & Toxicology, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
² Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China.
³ Innovation Institute for Artificial Intelligence in Medicine, Zhejiang University, Hangzhou 310058, China.
⁴ Cancer Center of Zhejiang University, Hangzhou 310058, China.

Abstract

Synthetic lethality is a proven effective antitumor strategy that has attracted great attention. Large-scale screening has revealed many synthetic lethal genetic phenotypes, and relevant small-molecule drugs have also been implemented in clinical practice. Increasing evidence suggests that CDKs, constituting a kinase family predominantly involved in cell cycle control, are synthetic lethal factors when combined with certain oncogenes, such as MYC, TP53, and RAS, which facilitate numerous antitumor treatment options based on CDK-related synthetic lethality. In this review, we focus on the synthetic lethal phenotype and mechanism related to CDKs and summarize the preclinical and clinical discoveries of CDK inhibitors to explore the prospect of CDK inhibitors as antitumor compounds for strategic synthesis lethality in the future.

Keywords: Antitumor therapy; Cyclin-dependent kinase; MYC; Oncogenes; P53; PARP; RAS; Synthetic lethality.

Publication types

Review