I heard back from Dr. Cortes regarding Pioglitazone. He said he is well aware of the research and studies are under way. Regarding fasting, he had no comment.
Regarding fasting effects on cancer:
There is discussion whether a multi-day fast 2 or 3 day (3 day emerging as more effective) vs a low carb (<20g) low calorie "fasting mimicking diet" is more effective. Both seem to be necessary to maximize benefit.
What is clear is that dramatic reduction in calories and elimination of carbs as a fuel source causes enzymatic changes in the body which re-direct the bodies resources. Older cells, primarily immune system cells, are canabalized to provide building blocks for ongoing systems. Most importantly - cancer protecting T-cells (Tregs) are discharged away from cancer tumor sites (and this includes the bone marrow where LSC's congregate).
To be clear - it's not the diet alone that coaxes LSC's to divide thereby making them vulnerable to TKI attack. It's the combination of fasting to first rid LSC's of their protective Treg cells (which then allows the immune system to attack them via autophagy) and then when the fast is broken, gene activation occurs which signals the bone marrow stem cells to get busy diving to replenish the scavenged older blood cells. It is this replenishment signal coupled with Treg removal that, in theory, opens LSC's to dramatic destruction by our rejuvenated immune system AND TKI attack.
Although I did make it two days (water only fast) and I remain in ketosis (little to zero carbs) for more than a week now, I will try going for a full 3 days water only fast to more fully test this idea. In my case, as I am already PCRU, I won't know if this is working. Only by stopping Sprycel and test for treatment free remission (and succeed) will I suspect this approach has worked.
It will take years of clinical trial study to prove that fasting plus TKI eliminates LSC's. Since fasting is probably good to do anyway from time to time, and the current science is promising - I feel it's worth trying now and not wait for clinical proof. The only thing Iwe have to lose are a few pounds. And that's a benefit in its own right.
For those of us who are not PCRU and are struggling to lower PCR levels, adding a fasting program (3 days no food - followed by low carb Ketosis diet), to test this idea, they might be able to let us know if it works for them. It would be a remarkable finding among ourselves to see a small group of CML Support group members who have been unable to lower their PCR's (i.e. plateaued) and then after trying this approach, experienced a sudden drop in their PCR. Although not scientific - it would be prroof enough for me. No one should attempt this fasting program without consulting a doctor. Electrolyte balance is important and TKI's do stress the heart.
One caveat for women -
There does seem to be a gender difference in how the sexes react to "starvation". Women are more prone to negative reaction to fasting than men. Something to consider.
Dr. Longo summarized his findings this way:
“It may be that by always being exposed to so much food, we are no longer taking advantage of natural protective systems which allow the body to kill cancer cells,” Longo said. “But by undergoing a fasting-mimicking diet, you are able to let the body use sophisticated mechanisms able to identify and destroy the bad but not good cells in a natural way.”
In answer to your question - a fasting mimicking diet may be all that is necessary to trigger this important cancer killing process.