Exploring Lipid Metabolism Pathways in Endometrial Cancer Growth and Metastasis
Metabolic disorders such as obesity and dyslipidemia are closely linked to diagnosis and risk of endometrial cancer (EC). With incidence and mortality rates on the rise, a study in Cell Communication and Signaling analyzed how lipid metabolism reprogramming contributes to EC progression and explored novel therapeutic strategies targeting these metabolic pathways.
Abnormal lipid uptake, enhanced de novo lipogenesis, and disrupted catabolism are key pathways in lipid metabolism that play significant roles in EC. With lipid uptake, proteins such as CD36, FABP, and LDLR, fuel tumor growth, invasiveness, and migration. However, their role in early-stage EC remains unclear, as some studies suggest that glucose may be the primary energy source during early disease stages. Enhanced lipogenesis, facilitated by enzymes such as ACLY, FASN, and SCD1, plays a critical role in tumor proliferation and metastasis. Additionally, disruptions in lipid catabolism, such as increased fatty oxidation (FAO) and cholesterol efflux, provide energy for tumor survival and help maintain cholesterol homeostasis.
Therapeutic strategies targeting lipid metabolism are emerging as promising interventions for EC. FASN inhibitors and HMGCR inhibitors are drugs targeting key enzymes that have shown antitumor activity in preclinical and early clinical studies. Other inhibits targeting SCD1 and SQLE have also shown potential in reducing tumor growth and metastasis. Ongoing clinical trials are evaluating the efficacy of targeting lipid metabolism in combination with immunotherapy or hormonal therapy.
Despite these advancements, further research is needed to identify the precise roles of lipid uptake and catabolism in EC initiation and progression and to evaluate the effectiveness of combination therapies. Because lipid metabolism and endometrial cancer are so closely linked, the researchers state that targeting these metabolic pathways could reduce tumor burden, prevent cancer progression, and improve patient survival.
“Lipid metabolism reprogramming plays an important role in tumor initiation and cancer progression of endometrial cancer,” the researchers concluded. “Targeting the core and transcriptional factors of lipid metabolism pathway alone or in combination with immunotherapy/hormone treatment is expected to decrease the tumor burden and provide promising treatment opportunity for patients with advanced/metastatic endometrial cancer.”
Reference
Wang X, Li Y, Hou X, Li J, Ma X. Lipid metabolism reprogramming in endometrial cancer: biological functions and therapeutic implications. Cell Commun Signal. 2024;22(1):436. doi:10.1186/s12964-024-01792-7.
