Dual RNA Polymerase I Inhibition with CX-5461 and BMH-21 Synergizes in Breast Cancer by Activating p53-Dependent Stress.

ABSTRACT: Hyperactivated ribosomal RNA (rRNA) transcription by RNA polymerase I (Pol I) is a hallmark of cancer and drives elevated ribosome biogenesis required for rapid tumor growth. Several Pol I inhibitors have been identified that induce potent anti-cancer effects. However, clinical application of the first-in-class Pol I inhibitor, CX-5461, has been limited by patient toxicity, which is comparable to other chemotherapies. Identifying synergistic drug combinations offers a promising strategy to maintain on-target anti-cancer effects while minimizing adverse reactions. Synergistic drug combinations involve drugs that enhance each other's effect, enabling dose reduction while preserving efficacy. Synergistic drug combinations of Pol I inhibitors and other anti-cancer agents have been reported; ho

SUBMITTER: Chung JY 

PROVIDER: S-EPMC12667773 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature