Targeting CDK2 in cancer: challenges and opportunities for therapy

Solomon Tadesse; Abel T Anshabo; Neil Portman; Elgene Lim; Wayne Tilley; C Elizabeth Caldon; Shudong Wang

doi:10.1016/j.drudis.2019.12.001

Targeting CDK2 in cancer: challenges and opportunities for therapy

Drug Discov Today. 2020 Feb;25(2):406-413. doi: 10.1016/j.drudis.2019.12.001. Epub 2019 Dec 10.

Authors

Solomon Tadesse¹, Abel T Anshabo², Neil Portman³, Elgene Lim³, Wayne Tilley⁴, C Elizabeth Caldon⁵, Shudong Wang⁶

Affiliations

¹ Centre for Drug Discovery and Development, University of South Australia Cancer Research Institute, Adelaide, SA 5000, Australia; Departement of Pharmaceutical Chemistry and Pharmacognosy, School of Pharmacy, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia.
² Centre for Drug Discovery and Development, University of South Australia Cancer Research Institute, Adelaide, SA 5000, Australia.
³ Garvan Institute of Medical Research, The Kinghorn Cancer Centre, Darlinghurst, NSW 2010, Australia; St Vincent's Clinical School, UNSW Sydney, Darlinghurst, NSW 2010, Australia.
⁴ Adelaide Medical School, The University of Adelaide, SA 5001, Australia.
⁵ Garvan Institute of Medical Research, The Kinghorn Cancer Centre, Darlinghurst, NSW 2010, Australia; St Vincent's Clinical School, UNSW Sydney, Darlinghurst, NSW 2010, Australia. Electronic address: [email protected].
⁶ Centre for Drug Discovery and Development, University of South Australia Cancer Research Institute, Adelaide, SA 5000, Australia. Electronic address: [email protected].

PMID: 31839441
DOI: 10.1016/j.drudis.2019.12.001

Abstract

Cyclin-dependent kinase 2 (CDK2) plays a pivotal part in cell cycle regulation and is involved in a range of biological processes. CDK2 interacts with and phosphorylates proteins in pathways such as DNA damage, intracellular transport, protein degradation, signal transduction, DNA and RNA metabolism and translation. CDK2 and its regulatory subunits are deregulated in many human cancers and there is emerging evidence suggesting CDK2 inhibition elicits antitumor activity in a subset of tumors with defined genetic features. Previous CDK2 inhibitors were nonspecific and limited by off-target effects. The development of new-generation CDK2 inhibitors represents a therapeutic opportunity for CDK2-dependent cancers.

Publication types

Review

MeSH terms

Animals
Antineoplastic Agents / pharmacology
Antineoplastic Agents / therapeutic use*
Biomarkers / metabolism
Cyclin-Dependent Kinase 2 / antagonists & inhibitors*
Cyclin-Dependent Kinase 2 / metabolism
Drug Therapy, Combination
Humans
Neoplasms / drug therapy*
Neoplasms / metabolism

Substances

Antineoplastic Agents
Biomarkers
Cyclin-Dependent Kinase 2