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Targeting a key driver of cancer

Reporter: Larry H. Bernstein, MD, FCAP

Again and again, we talk about “mutant genes”, when it frequently and almost inevitably gets to protein structure, as in this case. The protein in this case, and in similar cases behaves as an enzyme with an active site. In this case the binding affinity to the coenzyme is so strong that the conversion of GTP is arrested, with downstream consequences. This is somewhat different than other cancers in that the proliferative malignant neoplasia shows up so early. However, in many cancers, depending on tissue, there are progressive metabolic changes, and the mutation(s) come in later transitions. This may be adaptive, and it has to involve local circulation, proinflammatory effects, and mitochondrial function that gives way to reversal from catabolic to anabolic activity (reduced ATP production), which leads to reliance on the Warburgh – Pasteur effect. Further progression results in the cannabolization of peripheral muscle by gluconeogenesis to provide glucose. It is really encouraging to come to a step in the analysis where they have gotten back to protein structure and function in this very complicated disease state.