Mechanistic Roles of Transcriptional Cyclin-Dependent Kinases in Oncogenesis: Implications for Cancer Therapy.

Cyclin-dependent kinases (CDKs) are pivotal in regulating cell cycle progression and transcription, making them crucial targets in cancer research. The two types of CDKs that regulate different biological activities are transcription-associated CDKs (e.g., CDK7, 8, 9, 12, and 13) and cell cycle-associated CDKs (e.g., CDK1, 2, 4, and 6). One characteristic of cancer is the dysregulation of CDK activity, which results in unchecked cell division and tumor expansion. Targeting transcriptional CDKs, which control RNA polymerase II activity and gene expression essential for cancer cell survival, has shown promise as a therapeutic approach in recent research. While research into selective inhibitors for transcriptional CDKs is ongoing, inhibitors that target CDK4/6, such as palbociclib and ribociclib, have demonstrated encouraging outcomes in treating breast cancer. CDK7, CDK8, and CDK9 are desirable targets for therapy since they have shown oncogenic roles in a variety of cancer types, such as colorectal, ovarian, and breast malignancies. Even with significant advancements, creating selective inhibitors with negligible off-target effects is still difficult. This review highlights the need for more research to optimize therapeutic strategies and improve patient outcomes by giving a thorough overview of the non-transcriptional roles of CDKs in cancer biology, their therapeutic potential, and the difficulties in targeting these kinases for cancer treatment.