KRAS: feeding pancreatic cancer proliferation

• KRAS is the most frequently mutated gene in PDAC and drives cancer development and growth.
• Oncogenic KRAS alters cellular glucose uptake, glycolytic flux, and glutamine usage.
• Autophagy and macropinocytosis are upregulated by mutant KRAS to assist PDAC survival.
• Mechanisms of oncogenic KRAS-driven metabolism may yield new anti-K-Ras therapeutics.

Oncogenic KRAS mutation is the signature genetic event in the progression and growth of pancreatic ductal adenocarcinoma (PDAC), an almost universally fatal disease. Although it has been appreciated for some time that nearly 95% of PDAC harbor mutationally activated KRAS, to date no effective treatments that target this mutant protein have reached the clinic. A number of studies have shown that oncogenic KRAS plays a central role in controlling tumor metabolism by orchestrating multiple metabolic changes including stimulation of glucose uptake, differential channeling of glucose intermediates, reprogrammed glutamine metabolism, increased autophagy, and macropinocytosis. We review these recent findings and address how they may be applied to develop new PDAC treatments.