New Insights Into CDK12 Gene Inactivation as a Key Driver of Aggressive Ovarian Cancer

A recent groundbreaking study has shed light on the genetic factors underlying one of the most aggressive forms of ovarian cancer, highlighting the significant role of the CDK12 gene. High-grade serous carcinoma, which is the most prevalent ovarian cancer subtype, typically originates in the fallopian tubes before spreading to the ovaries and surrounding organs. Often diagnosed at an advanced stage, this cancer frequently develops resistance to existing chemotherapies, complicating treatment efforts. The complex genetics involve multiple alterations, including the involvement of the CDK12 gene.

Researchers from the University of Michigan Rogel Cancer Center utilized a genetically engineered mouse model to explore CDK12's role. Their findings revealed that CDK12 functions as a tumor suppressor gene; its inactivation accelerates tumor growth and leads to more aggressive disease progression. The study demonstrated that when CDK12 is disrupted, tumors in mice grow faster, and overall survival is reduced. Importantly, the model resembled human disease characteristics, including tumor appearance, genetics, immune microenvironment, and progression timing.

Additionally, the research uncovered that losing CDK12 activity triggers an immune response, recruiting immune T cells to the tumor environment. A key discovery was the identification of CDK13 as a potential partner gene; targeting this gene with a specific degrader, in combination with immune checkpoint inhibitors, significantly reduced tumor growth in the mice. This suggests that combination therapies involving CDK12/13 inhibitors and immunotherapies could offer new hope for treating resistant ovarian cancers.

The study's authors emphasized the urgent need for novel treatments, as many patients with high-grade serous carcinoma experience poor outcomes once resistance to standard chemotherapy develops. CDK12 has also been implicated in aggressive prostate cancers, indicating its broader relevance across different tumor types. Currently, several CDK12/13 inhibitors are under development, including those by the University of Michigan team, with plans to advance these candidates into clinical trials.

Overall, this research not only clarifies CDK12’s tumor suppressor role but also opens new avenues for targeted therapy in ovarian and possibly other cancers, offering hope for improved patient survival and treatment effectiveness.

Source: https://medicalxpress.com/news/2025-06-cdk12-gene-inactivation-key-driver.html