Emerging perspectives on metabolic reprogramming in the microenvironment of ovarian cancer metastasis

Abstract

Ovarian cancer (OC) is one of the most lethal malignancies in females, mainly due to the aggressive metastasis at the late stage and the unsatisfactory of current therapies. OC cells exhibit a special metastatic behavior compared to other common epithelial tumors, primarily spreading within the peritoneal cavity. Due to the complexity of tumor microenvironment, physical factors induce significant metabolic changes in OC cells, thereby enhancing their metastatic ability. Key cellular components, such as cancer-associated fibroblasts and adipocytes, act synergistically to support metastasis through metabolic interactions. Recent efforts in tumor immunometabolism showed that metabolic reprogramming of immune cells can also significantly impact metastatic progression. Moreover, the microbiome and cellular senescence are emerging as important factors that alter the metabolic landscape. This review provides a systematic review of metabolic reprogramming in the OC microenvironment and highlights the most recent clinical trials targeting metabolic pathways. By increasing our understanding of these metabolic interactions, we can develop innovative metabolism-targeting interventions for this devastating gynecological malignancy.