CDK9 inhibitors for the treatment of solid tumors
- PMID: 39127153
- PMCID: PMC11580798
- DOI: 10.1016/j.bcp.2024.116470
CDK9 inhibitors for the treatment of solid tumors
Abstract
Cyclin-dependent kinase 9 (CDK9) regulates mRNA transcription by promoting RNA Pol II elongation. CDK9 is now emerging as a potential therapeutic _target for cancer, since its overexpression has been found to correlate with cancer development and worse clinical outcomes. While much work on CDK9 inhibition has focused on hematologic malignancies, the role of this cancer driver in solid tumors is starting to come into focus. Many solid cancers also overexpress CDK9 and depend on its activity to promote downstream oncogenic signaling pathways. In this review, we summarize the latest knowledge of CDK9 biology in solid tumors and the studies of small molecule CDK9 inhibitors. We discuss the results of the latest clinical trials of CDK9 inhibitors in solid tumors, with a focus on key issues to consider for improving the therapeutic impact of this drug class.
Keywords: CDK9; Cancer therapeutics; Solid tumors; _targeted therapy.
Copyright © 2024 Elsevier Inc. All rights reserved.
Conflict of interest statement
Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Similar articles
-
Recent Developments in the Biology and Medicinal Chemistry of CDK9 Inhibitors: An Update.J Med Chem. 2020 Nov 25;63(22):13228-13257. doi: 10.1021/acs.jmedchem.0c00744. Epub 2020 Sep 17. J Med Chem. 2020. PMID: 32866383 Review.
-
CDK9 inhibitors in acute myeloid leukemia.J Exp Clin Cancer Res. 2018 Feb 23;37(1):36. doi: 10.1186/s13046-018-0704-8. J Exp Clin Cancer Res. 2018. PMID: 29471852 Free PMC article. Review.
-
A kinase inhibitor screen identifies a dual cdc7/CDK9 inhibitor to sensitise triple-negative breast cancer to EGFR-_targeted therapy.Breast Cancer Res. 2019 Jul 1;21(1):77. doi: 10.1186/s13058-019-1161-9. Breast Cancer Res. 2019. PMID: 31262335 Free PMC article.
-
Perspective of cyclin-dependent kinase 9 (CDK9) as a drug _target.Curr Pharm Des. 2012;18(20):2883-90. doi: 10.2174/138161212800672750. Curr Pharm Des. 2012. PMID: 22571657 Free PMC article. Review.
-
_targeting CDK9 for treatment of colorectal cancer.Mol Oncol. 2019 Oct;13(10):2178-2193. doi: 10.1002/1878-0261.12559. Epub 2019 Aug 21. Mol Oncol. 2019. PMID: 31398271 Free PMC article.
References
-
- Lapenna S and Giordano A, Cell cycle kinases as therapeutic _targets for cancer. Nat Rev Drug Discov, 2009. 8(7): p. 547–66. - PubMed
-
- Shore SM, et al., Identification of a novel isoform of Cdk9. Gene, 2003. 307: p. 175–82. - PubMed
-
- Liu H and Herrmann CH, Differential localization and expression of the Cdk9 42k and 55k isoforms. J Cell Physiol, 2005. 203(1): p. 251–60. - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Miscellaneous