An unexpected twist in cancer metabolism

Reason for the exclamation point: the conversion of PEP -> pyruvate is is considered the last of 3 rate-limiting steps in glycolysis. They propose an end-run around this rate-limiting step. In their model, PEP donates its phosphate to PGAM1. Thus, PEP becomes pyruvate. Normally I wouldn't expect this to be a meaningful way to produce pyruvate--but their data appear to support the notion that PGAM1 becomes dephosphorylated at a high enough rate that this process can repeat itself fast enough to sustain pyruvate production. Oh, and phosphorylated PGAM1 isn't just a temporary phosphate holder--they hypothesize (relying on other studies) that it helps shunt carbons into biosynthetic pathways (which you need if you are a proliferating cancer).

It's not every day that someone figures out how living cells bypass a canonical rate-limiting step in the fundamental metabolic process shared by all living things.

The first thing I thought was that starving the cells of sugar could be an effective treatment. Maybe feeding patients something like the ketogenic diet for epileptics (ie lots and lots of heavy cream and not much else esp. not many carbs) would help. A quick pub med search turns up a little bit of work in this area but there might be room for more.

I say this because, for example, leukemia is not one cancer; it is a constellation of cancers with similar features. However, if you take one specific cancer from this group (chronic myelogenous leukemia of the Bcr/abl type), you can treat it with imatinib. The survival at 5 years with imatinib is 89%--an incredible success. I'm saying this to point out that we already have individualized treatments for (a vanishing minority of) cancers.

As we grow to understand the molecular and genetic basis for each individual cancer, we will, one by one, be able to target these and turn them into chronic diseases like hypertension or hypercholesterolemia. Perhaps, one day, we will even cure them. The current article being discussed actually hints at a more global phenomenon, and may produce tools that we can use as add-ons to the individualized cancer treatments that we will be giving patients.

I'll just repeat the two things that I always like to say in this type of discussion:

1: We need to target the molecular basis for disease.

2: We need to remember the HAART model when treating cancer, which involves targeting multiple enzymes necessary for tumor growth and proliferation (or at least target different parts of the same enzymes) in order to fight drug resistance.