Researchers at the University of Michigan Rogel Cancer Center have uncovered the critical role of the gene CDK12 in driving an aggressive form of ovarian cancer. Published in the Proceedings of the National Academy of Sciences, their study reveals that CDK12 acts as a tumor suppressor, and its inactivation accelerates tumor growth. The findings also highlight a potential therapy targeting CDK12 and its partner gene, CDK13, which could pave the way for more effective treatments.
High-grade serous carcinoma, the most common type of ovarian cancer, often originates in the fallopian tubes and spreads aggressively. Current treatments frequently fail as the cancer develops resistance to chemotherapy. The new study used a genetically engineered mouse model to demonstrate that CDK12 inactivation leads to faster tumor growth and poorer survival outcomes.
The research team, led by Dr. Arul M. Chinnaiyan and Dr. Kathleen R. Cho, discovered that CDK12 inactivation not only fuels tumor growth but also triggers an immune response, recruiting T cells to the tumor site. This finding suggests that combining CDK12/13 degraders with immune checkpoint inhibitors could be a promising treatment strategy.
Dr. Cho emphasized the challenges in treating this cancer, noting that once resistance to first-line chemotherapy develops, options are limited. “New treatments are sorely needed,” she said, as survival rates remain low.
Dr. Chinnaiyan explained, “This is the first demonstration in a mouse model that CDK12 plays a tumor suppressor role in this type of cancer. Inactivating it leads to more aggressive disease.” Dr. Cho added, “Credentialing the mouse model was critical to ensuring it mirrors human cancer biology, a process that is both time-consuming and essential.”
The study not only advances understanding of ovarian cancer but also bridges insights from prostate cancer, where CDK12 has similarly been linked to aggressive disease. While the research is preclinical, the team aims to develop CDK12/13 degraders for clinical trials, offering hope for future therapies. Patients are advised that these treatments are not yet available, and current clinical trial information can be found through Michigan Medicine.
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