Metabolic reprogramming in breast cancer: Pathways driving progression, drug resistance, and emerging therapeutics
Pankaj Garg, Gargi Singhal, David Horné, Ravi Salgia, Sharad S. Singhal
Abstract
Breast cancer (BC), one of the most frequent causes of cancer-related death in women, is known to be a highly heterogeneous disease in regard to molecular subtypes, which seem to possess different metabolic profiles. Aberrant metabolism is well understood as one of the hallmarks of cancer and it contributes to BC progression, therapeutic resistance, and metastasis. Here, we analyze BC metabolism and how certain cancer types, such as hormone receptor-positive, HER2-positive, and triple-negative BC, use glycolysis, lipid metabolism, amino acid compulsion, and mitochondrial biogenesis to feed and proliferate. These metabolic hallmarks, in the context of the tumor microenvironments, are illustrated to highlight the metabolic byproducts that are derived from reprogrammed pathways and are vital to immunosuppression and tumor survival under low oxygen and nutrient availability. Furthermore, we emphasize novel trends in anticancer drugs designed to strike on these metabolic dependencies to suppress tumor growth. In addition to summing up current knowledge about metabolic reprogramming in BC, this review reveals new targets for specific treatments that might enhance prognosis in certain types of BC. This review aims to bridge basic scientific insights and clinical perspectives, guiding future metabolic interventions in BC toward clinically relevant, subtype-specific therapeutic strategies.