Nutrient Levels and Nutrient Sources in Pancreatic Tumors

It has been known that poor tumor perfusion and dysregulated cancer cell metabolism give rise to tumor microenvironments with unphysiologic nutrient levels, but the precise alterations in metabolite abundance are not well defined. In a 2015 study in Cancer Research, Kamphorst and colleagues published a detailed comparison of the metabolome from human pancreatic tumors and benign tissues. Tumors were depleted in glucose and various nonessential amino acids but, surprisingly, enriched in essential amino acids. The authors attributed these nutrient imbalances to macropinocytosis of extracellular proteins, a RAS-driven amino acid acquisition pathway that was found to be increased in human tumors and supports pancreatic cancer cell growth during amino acid starvation. These findings substantially contributed to the understanding of altered nutrient levels in tumors and extracellular proteins as noncanonical nutrients. Intratumoral nutrient levels in different cancer contexts and signaling pathways that regulate nutrient acquisition by cancer cells remain a focus of current research. See related article by Kamphorst and colleagues, Cancer Res 2015;75:544-53.