Metabolic networks in mutant KRAS-driven tumours: tissue specificities and the microenvironment

This Review examines the tissue-specific metabolism and associated therapeutic vulnerabilities of mutant KRAS-driven tumours, providing a comparative discussion of intrinsic metabolism, co-occurring mutations and metabolic interactions in the microenvironment in colorectal, lung and pancreatic cancer. Oncogenic mutations in KRAS drive common metabolic programmes that facilitate tumour survival, growth and immune evasion in colorectal carcinoma, non-small-cell lung cancer and pancreatic ductal adenocarcinoma. However, the impacts of mutant KRAS signalling on malignant cell programmes and tumour properties are also dictated by tumour suppressor losses and physiological features specific to the cell and tissue of origin. Here we review convergent and disparate metabolic networks regulated by oncogenic mutant KRAS in colon, lung and pancreas tumours, with an emphasis on co-occurring mutations and the role of the tumour microenvironment. Furthermore, we explore how these networks can be exploited for therapeutic gain.