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.
Marikki Laiho, MD, PhD (Johns Hopkins University)
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).