Detection of <i>CDK12-</i>LOF genomic alterations and their association with FTDs in a diverse spectrum of malignancies suggests that immunotherapy approaches targeting FINAs derived from <i>CDK12-</i>associated FTDs may be a broadly applicable strategy that could be explored across cancer types in a tumor-agnostic manner.
The RNA polymerase II (RNAPII) C-terminal domain kinase, CDK12, regulates genome stability, expression of DNA repair genes, and cancer cell resistance to chemotherapy and immunotherapy.
Here, we demonstrate that CDK12 promotes tumor initiation as a novel regulator of cancer stem cells (CSCs) and induces anti-HER2 therapy resistance in human breast cancer.
Herein, we discuss the present literature on CDK12 in cell function and human cancer, highlighting important roles for CDK12 as a clinical biomarker for treatment response and potential as an effective therapeutic target.
We propose that CDK12 is a tumor suppressor of which the loss-of-function mutations may elicit defects in multiple DNA repair pathways, leading to genomic instability underlying the genesis of the cancer.