Recent progress in development of cyclin-dependent kinase 7 inhibitors for cancer therapy

ABSTRACT

Introduction: Cyclin-dependent kinase 7 (CDK7) is a part of the CDK-activating kinase family (CAK) which has a key role in the cell cycle and transcriptional regulation. Several lines of evidence suggest that CDK7 is a promising therapeutic target for cancer. CDK7 selective inhibitors such as SY-5609 and CT7001 are in clinical development.

Areas covered: We explore the biology of CDK7 and its role in cancer and follow this with an evaluation of the preclinical and clinical progress of CDK7 inhibitors, and their potential in the clinic. We searched PubMed and ClinicalTrials to identify relevant data from the database inception to 14 October 2020.

Expert opinion: CDK7 inhibitors are next generation therapeutics for cancer. However, there are still challenges which include selectively, side effects, and drug resistance. Nevertheless, with ongoing clinical development of these inhibitors and greater analysis of their target, CDK7 inhibitors will become a promising approach for treatment of cancer in the near future.

KEYWORDS:

• Cyclin dependent kinase 7
• anti-cancer
• transcriptional addiction
• cell cycle
• CDK7 inhibitor

Article highlights

• The unique dual role of CDK7 in cell cycle and transcription is crucial for a range of tumors.

• CDK7-dependent transcriptional addiction provides a new opportunity for development of small molecular anti-cancer drugs.

• Combined therapy of CDK7 inhibitors and other drugs show good anti-cancer activities.

• CDK7 inhibitors still face the challenges of target selectivity and possible side effects in clinical applications.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

This work was funded by the National Natural Science Foundation of China [No. 81874288 and 82003590], Shandong Provincial Natural Science Foundation [ZR2019LZL004], the China-Australia Centre for Health Sciences Research [CACHSR no. 2019GJ07] and Young Scholars Program of Shandong University.