When researchers at the University of Michigan Rogel Cancer Center first identified a new subtype of aggressive prostate cancer, they knew they needed to understand how this genetic alteration was driving cancer and how to target it with treatment. In two new papers, both published in Cell Reports Medicine , they do both, describing the mechanisms of how alterations in the CDK12 gene drive prostate cancer development and reporting on a promising degrader that targets CDK12 and a related gene to destroy tumors. Researchers previously found loss of the CDK12 gene in about 7% of patients with metastatic prostate cancer, suggesting this alteration may be linked to a more-aggressive form of the disease.
This was discovered from DNA and RNA sequencing from patient tumor samples. CDK12 also plays a role in some ovarian cancers. To understand how CDK12 loss impacts cells on a molecular level, researchers created a mouse model to try to parallel the genetic alterations they were seeing in human prostate cancers.
What was quite surprising was when we created CDK12 loss in a mouse prostate, this caused precursor lesions to form in the mouse prostate. Then, when we added loss of the p53 oncogene, the mice developed bona fide invasive prostate cancer. It will be an addition to the field to have a genetically engineered mouse model that parallels what we see in human prostate cancer.
" Arul M. Chinnaiyan, M.D.
, Ph.D., senior author, director of the Michigan Center for Translational Patholog.
