Targeting metabolic reprogramming in KRAS-driven cancers

AbstractMutations ofKRAS are found in a variety of human malignancies, including in pancreatic cancer, colorectal cancer, and non-small cell lung cancer at high frequency. To date, no effective treatments that target mutant variants ofKRAS have been introduced into clinical practice. In recent years, a number of studies have shown that the oncogeneKRAS plays a critical role in controlling cancer metabolism by orchestrating multiple metabolic changes. One of the metabolic hallmarks of malignant tumor cells is their dependency on aerobic glycolysis, known as the Warburg effect. The role of KRAS signaling in the regulation of aerobic glycolysis has been reported in several types of cancer.KRAS-driven cancers are characterized by altered metabolic pathways involving enhanced nutrients uptake, enhanced glycolysis, enhanced glutaminolysis, and elevated synthesis of fatty acids and nucleotides. However, Just how mutatedKRAS can coordinate the metabolic shift to promote tumor growth and whether specific metabolic pathways are essential for the tumorigenesis ofKRAS-driven cancers are questions which remain to be answered. In this context, the aim of this review is to summarize current data onKRAS-related metabolic alterations in cancer cells. Given that cancer cells rely on changes in metabolism to support their growth and survival, the targeting of metabolic processes may be a potential strategy for treatingKRAS-driven cancers.
Source: International Journal of Clinical Oncology - Category: Cancer & Oncology Source Type: research