Pre-surgical window study of metformin in obesity-driven endometrial cancer

Abstract

population was significantly more dormant than the original tumor. RNA sequencing analysis of treated and untreated PDX tumors (n = 6 pair) demonstrated that numerous factors with roles in ribosomal synthesis were significantly altered by treatment. In vitro, an inhibitor of ribosomal synthesis, CX-5461, caused significant G2/M-phase arrest, and effects were much more profound in chemoresistant cells than corresponding chemosensitive cells. In vivo, of the five PDX models that were treated with CX-5461, two had progression, one had stable disease, one had a 60% reduction in tumor growth, and one had a complete response to single-agent therapy, still without recurrence after 3 months. Conclusions: The ovarian PDX model exhibits similarity to patient tumors. Postchemotherapy tumors reveal severe alteration of ribosomal synthesis. Treatment with an inhibitor of ribosomal RNA synthesis was highly effective in vitro and in vivo, offering a novel opportunity to specifically target the chemoresistant population in ovarian cancer.