Med Hypotheses. 2008;70(2):419-23. Epub 2007 Jun 4.
PPAR gamma agonists can be expected to potentiate the efficacy of metronomic chemotherapy through CD36 up-regulation.
McCarty MF, Barroso-Aranda J, Contreras F.
Oasis of Hope Hospital, Tijuana, Mexico.
ability of metronomic chemotherapy to induce endothelial apoptosis has
been traced to increased endothelial expression of thrombospondin-1,
which activates endothelial CD36 receptors, triggering the extrinsic
apoptotic pathway. Endothelial expression of CD36 is variable. Recent
studies show that PPAR gamma agonists - previously shown to have
angiostatic activity - can markedly boost endothelial expression of
CD36, thereby potentiating the apoptotic response of endothelial cells
to thrombospondin-1-mimetic peptides. Thus, concurrent administration
of PPAR gamma agonists would be expected to enhance the efficacy of
metronomic chemotherapy. These considerations may help to rationalize
recent reports that a regimen consisting of low-dose trofosfamide,
pioglitazone, and a cox-2 inhibitor achieves tumor regression or
prolonged tumor stasis in a meaningful proportion of cancer patients.
The angiostatic efficacy of metronomic chemotherapy complemented by
PPAR gamma agonist administration would likely be potentiated by
ancillary measures that block the survival signals evoked by
endothelial growth factors such as VEGF or angiopoietin-1.