BACKGROUND
Cyclin-dependent kinase 9 (CDK9) is a central regulator of RNA polymerase II elongation and has emerged as a therapeutic target in tumors characterized by transcriptional addiction. Growing interest in selective inhibitors and targeted degraders has renewed attention to the translational potential of CDK9-directed therapy.
AREAS COVERED
This review summarizes the molecular functions of the CDK9/positive transcription elongation factor b (P-TEFb) axis, its role in super-enhancer-driven oncogenic programs, and the mechanisms by which CDK9 inhibition promotes apoptosis, epigenetic derepression, and tumor microenvironment remodeling. We also discuss representative small-molecule inhibitors and proteolysis-targeting chimera (PROTAC) degraders, emerging biomarkers for patient stratification, rational combination strategies, and the current landscape of resistance mechanisms.
EXPERT OPINION
Selective targeting of CDK9 offers a promising route for treating refractory malignancies, particularly when guided by transcriptional dependency, biomarker-informed dosing, and rational combination design. Future progress will likely depend on improving therapeutic index, refining translational biomarkers, and anticipating adaptive resistance during clinical development.
Tiyao Liu, Zhongran Liu, Wen-Jing Wei et al.· Expert opinion on therapeuti...· 0 citations
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Shaoqiang Wang, Linhao Zhang, Guiling Shi et al.· PLoS ONE· 0 citations
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Tiyao Liu, Shudong Wang, Baoming Feng et al.· Journal of Chemical Informat...· 0 citations