Epitranscriptomic Determinants of Treatment Resistance in Prostate Cancer

Principal Investigator: Nigel Mongan, PhD (University of Nottingham)

Co-Investigators: Corinne Woodcock (University of Nottingham), Nathan Archer, PhD (University of Nottingham), Rupert Fray, PhD (University of Nottingham), Victoria James, PhD (University of Nottingham), Jennie Jeyapalan, PhD (University of Nottingham), Jennifer Lothion-Roy BVM BVS (University of Nottingham), Anna Harris BSc (University of Nottingham)

Description:

• The androgen receptor (AR) is a primary driver of prostate cancer and is a key therapeutic target in patients with aggressive and advanced disease.  Unfortunately, resistance to AR-targeted therapy inevitably occurs.  Understanding the mechanisms of resistance and discovery of new ways to inhibit AR activity are urgently needed.
• Dr. Nigel Mongan and team have identified altered RNA methylation as a possible mechanism of resistance to the AR-targeted therapy enzalutamide.
• In this project, Dr. Mongan and team will investigate the roles of the RNA methylation in prostate cancer. The team previously found that RNA methylation plays a role in gene regulation in more aggressive prostate cancer.
• In this project, RNA methylation and its associations with clinical outcomes will be investigated in ethnically diverse prostate cancer cohorts from across the disease spectrum.
• Whether enzalutamide treatment alters the landscape of RNA methylation will be investigated in prostate cancer models.
• The team will also determine whether targeting RNA methylation may enhance the treatment efficacy of enzalutamide in preclinical prostate cancer models.
• If successful, this project will establish the role and potential of RNA methylation as a therapeutic target in prostate cancer.

What this means to patients:  Altered RNA methylation may contribute to treatment resistance in prostate cancer by changing the landscape of gene expression.  Dr. Mongan and team will determine whether aberrant regulation of RNA methylation is a driver of enzalutamide resistance, and whether therapies targeting RNA methylation may overcome enzalutamide resistance.  These data could lead to a new treatment strategy for patients with prostate cancer.