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http://www.cmleukemi...-inhibitor.html

Combination of pioglitazone with tyrosine kinase inhibitor 

Important notice: You must inform your CML doctor or a qualified doctor before using this drug. The material presented here is for information purposes only;  it is not a substitute for your physician's guidance and care. The side-effects of pioglitazone would also to be taken into account if this treatment were to be offered in routine care.  

" Philippe Leboulch, M.D., a professor of medicine and cell biology at the University of Paris, and colleagues temporarily administered pioglitazone in addition to imatinib to three patients with chronic myeloid leukemia.

Here we show that the residual CML LSC pool can be gradually purged by the glitazones, antidiabetic drugs that are agonists of peroxisome proliferator-activated receptor-γ (PPARγ). We found that activation of PPARγ by the glitazones decreases expression of STAT5 and its downstream targets HIF2α5 and CITED26, which are key guardians of the quiescence and stemness of CML LSCs.

When pioglitazone was given temporarily to three CML patients in chronic residual disease in spite of continuous treatment with imatinib, all of them achieved sustained CMR, up to 4.7 years after withdrawal of pioglitazone. This suggests that clinically relevant cancer eradication may become a generally attainable goal by combination therapy that erodes the cancer stem cell pool."

Extract of    Prost S, Relouzat F, Spentchian M, et al. Erosion of the chronic myeloid leukaemia stem cell pool by PPARγ agonists. Nature. 2015. doi:10.1038/nature15248


 
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