SUMMARY OF INVENTION
Although prostate cancer (PC) can be divided into molecularly distinct subtypes, there is no molecular classification system used clinically to identify patients with aggressive disease. For instance, the PCS and PAM50 classifications have been shown to segregate PC into distinct molecular subtypes but are not used clinically to guide treatment. Rather, the current classification of PC remains largely based on clinical and pathological characteristics.
Investigators previously have shown that ribonucleotide reductase subunit M2 (RRM2) is expressed at low levels in normal prostate tissue, but that increased expression is highly correlated with poor clinical outcomes in PC. Here, MSK investigators have identified RRM2 as a driver of the most aggressive molecular PC subtypes identified by PCS and PAM50 classifiers. Investigators have further established an RRM2 gene signature as well as multiple RRM2 sub-signatures that highly correlate with poor clinical outcomes as well as resistance to Xtandi (enzalutamide), an AR antagonist and the mainstay class of late-stage PC therapy.
- RRM2 signature specifically identifies the most aggressive PC subtypes with no overlap with less aggressive subtypes
- RRM2 panel superior to the commercially available Prosigna test (PAM50) at assessing risk
- 12-gene sub-signature identifies the core set of genes that control tumor progression and PC outcomes
- 12-gene panel also associated with poor outcomes in breast, ovarian, lung and liver cancers
- 11-gene panel derived from the RRM2 signature could be used to identify enzalutamide resistance in circulating tumor PC cells
Prostate cancer is the third leading cause of cancer death in the U.S. and is one of the most frequently diagnosed cancers in men. According to 2014-2016 data, approximately 11.6% of men will be diagnosed with prostate cancer at some point during their lifetime.
Mazzu YZ et al. (2019) A Novel Mechanism Driving Poor-Prognosis Prostate Cancer: Overexpressesion of the DNA Repair Gene, Ribonucleotide Reductase Small Subunit M2 (RRM2). Clin Cancer Res (PubMed link)
Provisional Application filed April 16, 2019
- Ying Mazzu, PhD, Senior Research Scientist, Laboratory of Philip Kantoff, MD
- Philip Kantoff, MD, Laboratory Head, Memorial Hospital Research Laboratories; Chair, Department of Medicine
Lisa Kennedy, PhD