Systemic Treatment for Metastatic Prostate Cancer by a Novel Small Molecule Targeting RNA Polymerase I

About Systemic Treatment for Metastatic Prostate Cancer by a Novel Small Molecule Targeting RNA Polymerase I
  • Discovering and targeting molecules and mechanisms that prostate cancer cells depend on is critical for the development of novel therapies that extend the lives of patients.
  • Dr. Laiho and team have found that prostate cancer cells have a significantly increased need for protein synthesis and the RNA Polymerase I molecule that governs these processes and have identified a molecule, BMH-21, that inhibits RNA Polymerase I.
  • Efficacy and treatment protocols will be tested for analogs of BMH-21 in mouse models of aggressive prostate cancer. Novel platforms will be developed to examine the functional activity of RNA Polymerase I and therapeutic responses to BMH-21.
  • The precise role of other proteins that cooperate with AR to regulate target genes during the progression of prostate cancer will be investigated.
  • BMH-21 may also inhibit prostate tumor growth by inhibiting the activity of the androgen receptor (AR), a primary driver of prostate cancer, and by altering the epigenetic state of cells. The mechanisms and consequences of BMH-21 treatment on these activities will be determined.

What this means for patients: Discovering new targets for prostate cancer therapy is a critical need. If successful, this project will define the mechanisms and preclinical efficacy of a therapeutic agent that targets protein synthesis in prostate cancer cells and will lead immediately into the initiation of clinical trials.

Principal Investigator:

Marikki Laiho, MD, PhD (Johns Hopkins University)

Co-investigators:

Charles Bieberich, PhD (University of Maryland Baltimore County), Angelo De Marzo, MD, PhD (Johns Hopkins: John Hopkins Medical Institutions), Srinivasan Yegnasubramanian, MD, PhD (Johns Hopkins: John Hopkins Medical Institutions), Sarah Wheelan, MD, PhD (Johns Hopkins: John Hopkins Medical Institutions), Paul Sirajuddin, PhD (Johns Hopkins: John Hopkins Medical Institutions).