Metabolic reprogramming and interventions in endometrial carcinoma

Cancer cells are usually featured by metabolic adaptations that facilitate their growth, invasion, and metastasis. Thus, reprogramming of intracellular energy metabolism is currently one of the hotspots in the field of cancer research. Whereas aerobic glycolysis (known as the Warburg effect) has long been considered a dominant form of energy metabolism in cancer cells, emerging evidence indicates that other metabolic forms, especially oxidative phosphorylation (OXPHOS), may play a critical role at least in some types of cancer. Of note, women with metabolic syndromes (MetS), including obesity, hyperglycemia, dyslipidemia, and hypertension, have an increased risk of developing endometrial carcinoma (EC), suggesting a close link between metabolism and EC. Interestingly, the metabolic preferences vary among EC cell types, particularly cancer stem cells and chemotherapy-resistant cells. Currently, it is commonly accepted that glycolysis is the main energy provider in EC cells, while OXPHOS is reduced or impaired. Moreover, agents specifically targeting the glycolysis and/or OXPHOS pathways can inhibit tumor cell growth and promote chemosensitization. For example, metformin and weight control not only reduce the incidence of EC but also improve the prognosis of EC patients. In this review, we comprehensively overview the current in-depth understanding of the relationship between metabolism and EC and provide up-to-date insights into the development of novel therapies targeting energy metabolism for auxiliary treatment in combination with chemotherapy for EC, especially those resistant to conventional chemotherapy.

Automated summary

Cancer cells often reprogram their energy metabolism to promote growth and invasion, with oxidative phosphorylation (OXPHOS) and glycolysis playing key roles. Metabolic syndromes in women, such as obesity and hyperglycemia, increase the risk of endometrial carcinoma (EC), which is characterized by altered metabolic preferences. Targeting glycolysis and OXPHOS pathways can inhibit tumor growth and sensitize EC cells to chemotherapy. This review provides an overview of the relationship between metabolism and EC and offers insights into the development of new therapies for chemotherapy-resistant EC.