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CDK10 in Gastrointestinal Cancers: Dual Roles as a Tumor Suppressor and Oncogene
Zainab A Bazzi1,2, Isabella T Tai1,2
1Division of Gastroenterology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada.
Abstract:
Cyclin-dependent kinase 10 (CDK10) is a CDC2-related serine/threonine kinase involved in cellular processes including cell proliferation, transcription regulation and cell cycle regulation. CDK10 has been identified as both a candidate tumor suppressor in hepatocellular carcinoma, biliary tract cancers and gastric cancer, and a candidate oncogene in colorectal cancer (CRC). CDK10 has been shown to be specifically involved in modulating cancer cell proliferation, motility and chemosensitivity. Specifically, in CRC, it may represent a viable biomarker and target for chemoresistance. The development of therapeutics targeting CDK10 has been hindered by lack a specific small molecule inhibitor for CDK10 kinase activity, due to a lack of a high throughput screening assay. Recently, a novel CDK10 kinase activity assay has been developed, which will aid in the development of small molecule inhibitors targeting CDK10 activity. Discovery of a small molecular inhibitor for CDK10 would facilitate further exploration of its biological functions and affirm its candidacy as a therapeutic target, specifically for CRC.
Insights
Cyclin-dependent kinase 10 (CDK10) plays dual roles in cancer. A new assay enables the development of CDK10 inhibitors, potentially targeting colorectal cancer chemoresistance.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- Cyclin-dependent kinase 10 (CDK10) is a serine/threonine kinase regulating cell proliferation, transcription, and cell cycle.
- CDK10 acts as a tumor suppressor in some cancers but an oncogene in colorectal cancer (CRC).
- CDK10 influences cancer cell proliferation, motility, and chemosensitivity, particularly in CRC where it may indicate chemoresistance.
Purpose of the Study:
- To address the lack of specific small molecule inhibitors for CDK10.
- To facilitate the development of therapeutics targeting CDK10 activity.
- To enable further exploration of CDK10's biological functions and therapeutic potential in CRC.
Main Methods:
- Development of a novel high-throughput screening assay for CDK10 kinase activity.
- Utilizing the assay to identify and develop small molecule inhibitors targeting CDK10.
Main Results:
- A novel CDK10 kinase activity assay has been successfully developed.
- This assay is poised to aid in the discovery of specific small molecule inhibitors for CDK10.
Conclusions:
- The developed assay is crucial for advancing CDK10-targeted therapeutics.
- Discovery of CDK10 inhibitors will facilitate research into its biological roles and therapeutic applications, especially for colorectal cancer chemoresistance.
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