The Sweet Spot of Targeting Tumor Metabolism in Ovarian Cancers

Simple Summary Ovarian cancer is the most lethal gynecologic malignancy. While most patients will initially respond to treatment, the majority will recur and develop chemoresistance. Therefore, we require a better understanding of how cancer cells evade chemotherapy, including the reprogramming of their signaling pathways in nutrient deficient environments. The aims of this review are to provide an overview of altered metabolism and signaling pathways in ovarian cancer and to outline potential therapeutic modalities to exploit these changes. The objective of this review is to explore the metabolomic environment of epithelial ovarian cancer that contributes to chemoresistance and to use this knowledge to identify possible targets for therapeutic intervention. The Warburg effect describes increased glucose uptake and lactate production in cancer cells. In ovarian cancer, we require a better understanding of how cancer cells reprogram their glycogen metabolism to overcome their nutrient deficient environment and become chemoresistant. Glucose metabolism in ovarian cancer cells has been proposed to be influenced by altered fatty acid metabolism, oxidative phosphorylation, and acidification of the tumor microenvironment. We investigate several markers of altered metabolism in ovarian cancer including hypoxia-induced factor 1, VEGF, leptin, insulin-like growth factors, and glucose transporters. We also discuss the signaling pathways involved with these biomarkers including PI3K/AKT/mTOR, JAK/STAT and OXPHOS. This review outlines potential metabolic targets to overcome chemoresistance in ovarian cancer. Continued research of the metabolic changes in ovarian cancer is needed to identify and target these alterations to improve treatment approaches.

Automated summary

Ovarian cancer is a highly lethal gynecologic malignancy with chemoresistance being a major challenge. This review highlights the altered metabolism and signaling pathways in ovarian cancer, as well as potential therapeutic strategies to overcome chemoresistance.