Mini-review: Limitations and Off-Target Effects of Tryptophan-Related IDO Inhibitors in Cancer Treatment, 2019, Gunther et al

https://www.frontiersin.org/articles/10.3389/fimmu.2019.01801/full

 

Tagging @RDP - might be of interest

 

As far as I understand:

What is happening with kynurenine and cancer cells with mutations that lead to a highly active kynurenine pathway can escape destruction by the immune system because activation of the kynurenine pathway has a local immunusuppressive effect.

There are attempts to develop drugs to suppress the activation of kynurenine pathway. It doesn't have anything to do with the metabolic trap hypothesis (which leads to an impairment of the kynurenine pathway).

 

The field of IDO1 inhibitors and cancer has been hot for years now, but as this Frontiers article highlights, most Pharma firms abandoned these programs with the first Phase 3 failure.

I was actually glad these drugs did not meet their clinical endpoint goals because I worried that they might cure cancer, but CAUSE ME/CFS if the IDO trap hypothesis is correct.

One of the valuable side products of this enormous effort by Pharma is that it produced vastly more research on IDO1 that we can draw on in the context of the trap. I'll talk about some of these benefits in the last few slides of my upcoming talk at the Stanford Symposium.