A team from Rice University’s Center for Theoretical Biological Physics (CTBP) and the Baylor College of Medicine says it has created a basic framework of how cancer cells—whether in tumors or as single cells—adapt when their attempts to metastasize are blocked by drugs or the body’s immune system. Understanding the cells’ strategies could someday help scientists design therapies that keep them in check. This confirms what we’ve been saying for years – cancer can change its metabolic pathway (the way it feeds) to stay alive, and the more aggresive a cancer is, may well be defined (in part) as the speed at which it can change its source of fuel.

Their model shows a direct connection between gene regulation and metabolic pathways and how cancer cells take advantage of it to adapt to hostile environments, a process known as metabolic plasticity.

1Rice University researchers—from left, Dongya Jia, PhD, Herbert Levine, PhD, and José Onuchic, PhD—detail a direct connection between gene expression and metabolism and how cancer cells take advantage of it to adapt to hostile environments.

Led by physicists Herbert Levine, PhD, and José Onuchic, PhD, and postdoctoral fellow Dongya Jia, PhD, the researchers looked at oxidative phosphorylation (OXPHOS) and glycolysis, metabolic processes that provide cells with the energy and chemical building blocks they need to proliferate. From their model, they detailed for the first time a direct association between the activities of two protein players, AMP-activated protein kinase (AMPK) and hypoxia-inducible factor-1 (HIF-1), the master regulators of OXPHOS and glycolysis, respectively, with the activities of three major metabolic pathways: glucose oxidation, glycolysis, and fatty acid oxidation. These are two genes that we check in all of our patients!

Their theoretical model was experimentally supported by Baylor cancer mitochondrial metabolism researchers led by Benny Abraham Kaipparettu, PhD. The group’s study (“Elucidating cancer metabolic plasticity by coupling gene regulation with metabolic pathways”) appears in the Proceedings of the National Academy of Sciences.

2“Metabolic plasticity enables cancer cells to switch their metabolism phenotypes between glycolysis and OXPHOS during tumorigenesis and metastasis. However, it is still largely unknown how cancer cells orchestrate gene regulation to balance their glycolysis and OXPHOS activities. Previously, by modeling the gene regulation of cancer metabolism we have reported that cancer cells can acquire a stable hybrid metabolic state in which both glycolysis and OXPHOS can be used. Here, to comprehensively characterize cancer metabolic activity, we establish a theoretical framework by coupling gene regulation with metabolic pathways,” wrote the investigators.

This is precisely why we’ve begun to experiment with changing a patient’s diet, rotationally, with aggresive cancers. One also needs to check and change both drug and nutraceutical approaches regularily as well. Fasting and Fasting Mimicking Diets may also be appropriate.

See more in our Cancer Diet section as well as Dr. Conners book, Cancer Genes.

The study: Elucidating cancer metabolic plasticity by coupling gene regulation with metabolic pathways