Targeting metabolic reprogramming in KRAS-driven cancers

• Published in: International journal of clinical oncology 2017-08, Vol.22 (4), p.651-659
• Main Authors: Kawada, Kenji, Toda, Kosuke, Sakai, Yoshiharu
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - genetics; Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Amino Acids - metabolism; Cancer; Cancer Research; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - pathology; Cell Transformation, Neoplastic - metabolism; Colorectal carcinoma; Colorectal Neoplasms - genetics; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - pathology; Fatty acids; Glucose - metabolism; Glycolysis; Glycolysis - physiology; Humans; K-Ras protein; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Lungs; Medicine; Medicine & Public Health; Metabolic disorders; Metabolic pathways; Metabolism; Molecular Targeted Therapy; Mutation; Non-small cell lung carcinoma; Nucleotides; Nutrients; Oncology; Pancreatic cancer; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - metabolism; Pancreatic Neoplasms - pathology; Proto-Oncogene Proteins p21(ras) - genetics; Proto-Oncogene Proteins p21(ras) - metabolism; Review Article; Signal Transduction; Surgical Oncology; Tumor cells; Tumorigenesis
• ISSN: 1341-9625; 1437-7772
• DOI: 10.1007/s10147-017-1156-4

Mutations of KRAS 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 of KRAS have been introduced into clinical practice. In recent years, a number of studies have shown that the oncogene KRAS 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 mutated KRAS can coordinate the metabolic shift to promote tumor growth and whether specific metabolic pathways are essential for the tumorigenesis of KRAS -driven cancers are questions which remain to be answered. In this context, the aim of this review is to summarize current data on KRAS -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 treating KRAS -driven cancers.