Mevalonate Metabolism in Cancer Stemness and Trained Immunity.

ABSTRACT

Mevalonate metabolism provides cancer and immune cells with diverse products to ensure cell functionality. Similar metabolic reprogramming that raises mevalonate metabolism to higher levels appears to drive both, epithelial mesenchymal transition (EMT) of cancer cells, a reverse differentiation program that generates cancer cells with stem cell properties, and immune cell training for increased responsiveness to secondary stimulation. In this review, we address how mevalonate metabolism supports cancer development and stemness on the one hand, and on the other promotes immune responsiveness. In view of this dual nature of mevalonate metabolism, strategies to manipulate this metabolic pathway as part of anti-cancer therapies require careful analysis of risks versus benefits.