Researchers have found that if one type of retinoblastoma (RB) susceptibility gene is removed, but not the other, large-scale genetic changes could occur that could make cancer both resistant to treatment and more likely to spread. The work comes from researchers at Thomas Jefferson University and was published earlier this week in The Journal of Clinical Investigation.
"RB loss causes a major reprogramming of gene expression, allowing induction of pathways that promote features that induce characteristics of lethal disease," said senior author Karen Knudsen, Ph.D.
To reach their findings, first author Christopher McNair, Ph.D., analyzed tumor samples and cell-free DNA samples from patients with advanced, lethal-stage prostate cancer. They found that the complete loss of the RB gene, rather than inactivation was associated with changes in the gene-networks that were linked to the agressive disease. Interestingly though, they found that the cancer-promoting program that RB-loss unleashed was distinct from the cell-cycle control genes that RB is best known for controlling.
This research demonstrates that RB status can be tracked using liquid biopsies in prostate cancer patient samples. The researchers believe the work will help create personalized therapies for each patient's cancer subtype.
"Unlike breast cancer, all prostate cancers are currently treated in an identical fashion. This discovery, and the clinical trials we have underway, suggest that RB status might be used as means to stratify patients into more effective treatment regimens," said William Kevin Kelly, leader of the Prostate Cancer Program at Sidney Kimmel Cancer Center.
Image: A circularized version of the human genome. Each subsequent inner ring represents novel findings in the study relevant to disease. Image courtesy of Christopher McNair at Thomas Jefferson University.