Combining P13K inhibitors with Keto diet for cancer.

[MateoBeach]

I missed this when it was published in Nature in July 2019 by Lewis Cantley. Mouse study but shows the relationship between P13K inhibitors and how a very low carbohydrate or ketogenic diet can allow them to work against cancer. They also compared metformin to the keto diet in this regard. It is pertinent because there are already 2 FDA approved P13K inhibitors. In 2014, FDA approved the first PI3K inhibitor, idelalisib (Zydelig®), to treat patients with relapsed follicular lymphoma. Copanlisib (Aliqopa} is now the second approved PI3K inhibitor.

The question is whether the metabolic changes induced by a keto diet can make P13K inhibitors effective against solid tumors. Anyone know of any such clinical trials?

dietdoctor.com/us-researche...

cancer.gov/news-events/canc...

[MateoBeach]

Here is a link to the abstract of the Nature article:

nature.com/articles/s41586-...

[MateoBeach]

OK, found a link to the full text of the article here:

ncbi.nlm.nih.gov/pmc/articl...

[pjoshea13 in reply to MateoBeach]

I see that one of the authors is Siddhartha Mukherjee (The Emperor of All Maladies: A Biography of Cancer) [1]

-Patrick

[1] en.wikipedia.org/wiki/Siddh...

[MateoBeach]

Some caveats to note: (And my musings are speculations not tested.)"It is important to note that treatment with the ketogenic diet alone had variable effects in different tumor models indicating that the dietary changes themselves were insufficient to cause the tumor responses observed across the murine models. In some instances, such as the AML model, the ketogenic diet alone accelerated disease progression suggesting that this diet may be detrimental for some cancer patients when used in isolation."

This raises questions about keto diet in predominantly fat metabolizing prostate cancer (usually earlier disease) vs glucose utilizing (usually later disease) when FDG scans positive.

And their final word:

"While these data do not exclude insulin-independent effects of combining PI3K inhibition with anti-glycemic therapy, they demonstrate that utilizing this approach has the potential to significantly increase the therapeutic efficacy of these compounds. In light of these results, it may also be important to think about how common clinical practices such as IV glucose administration, glucocorticoid use, or providing patients with glucose-laden nutritional supplements may impact therapeutic responses. As therapeutic agents that target this critical oncogenic pathway are brought through clinical trials, they should be paired with strategies such as SGLT2 inhibition or the ketogenic diet to limit this self-defeating systemic feedback."

[tango65]

Thanks for posting. This info may be useful to people whose cancers have PTEN loss, which is a common genetic defect. PTEN inhibits the PI3K pathway,

ncbi.nlm.nih.gov/pmc/articl...

Best of luck!!.