Research Offers Deeper Understanding of Role of Retinoblastoma Gene in Aggressive Prostate Cancer

(BY RACHEL DERITA, PhD Candidate,Thomas Jefferson University, Department of Cancer Biology) In prostate cancer, there is a continual effort to better stratify patients. Current standards of care for all patients are identical, but each case is not. A recent study (published on December 4, 2017 in the Journal of Cl inical Investigation) from Thomas Jefferson University’s Sidney Kimmel Cancer Center (SKCC) identified loss of the retinoblastoma (RB) susceptibility gene as a cause of what senior author Karen Knudsen, PhD, Director of the SKCC, describes as “major reprogramming of gene expression, allowing induction of pathways that promote features that induce characteristics of lethal disease.” That article is titled “Differential Impact of RB Status on E2F1 Reprogramming in Human Cancer.” RB was the first “gatekeeper” gene (genes that are responsible for controlling cell growth and keeping it in check) discovered for cancer. Loss or damage to RB allowed cancer to thrive and be more aggressive, but the exact mechanism of how this happened remained unclear. The JCI -piublshed study involved tumor and cell-free DNA analysis of samples from patients with” advanced, lethal-stage” prostate cancer from multiple institutions across the US and international institutions in the UK, Italy, Belgium, Finland, and Sweden. RB function may be disrupted in several different ways, but it was found that complete loss of the RB gene, compared to inactivation, was associated with the transcriptional reprogramming linked to aggressive disease. This reprogramming, interestingly, was unique and different from the typical cell-cycle genes that RB controls as a gatekeeper.
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