WASHINGTON, June 14 (Xinhua) -- Researchers have identified a new subtype of prostate cancer that occurs in about seven percent of patients with advanced disease but it is potentially more responsive to immunotherapy, according to a study published on Thursday in the journal Cell.
The subtype, characterized by loss of the gene CDK12, was found to be more common in metastatic prostate cancer compared to early stage tumors that had not spread.
"Because prostate cancer is so common, seven percent is a significant number. The fact that immune checkpoint inhibitors may be effective against this subtype of prostate cancer makes it even more significant," said the paper's senior study author Arul Chinnaiyan, director of the Michigan Center for Translational Pathology.
They looked at DNA and RNA sequencing data from 360 tumor samples from patients with metastatic castration-resistant prostate cancer, an aggressive, advanced form of the disease in which the cancer has spread throughout the body and no longer responds to traditional hormone-based treatments.
Researchers found loss of CDK12 in only about one percent of early prostate cancer samples, but it jumped to seven percent for metastatic cancer, which indicated a more-aggressive form of the disease.
"It suggests that those early stage patients who have CDK12 loss are the ones who will develop metastatic disease. This could be a harbinger in early cancer," said Chinnaiyan.
By following the mechanism of how CDK12 loss impacts the cell, researchers found a process in which cells create neoantigens that are foreign to the immune system. This boosts immune-fighting T-cells, which may explain why these patients benefit from immune checkpoint blockade.
According to the researchers, tumors in which CDK12 was inactivated were responsive to immune checkpoint inhibitors, a type of immunotherapy treatment that has overall had limited success in prostate cancer.
Researchers are expected to lead a multisite clinical trial to assess checkpoint inhibitors as a treatment for metastatic prostate cancer with CDK12 loss.
