Peroxisome proliferator-activated receptor-gamma (PPARγ) is a nuclear receptor acting
as a transcription factor involved in the regulation of energy metabolism, cell cycle, cell differentiation,
and apoptosis. These unique properties constitute a strong therapeutic potential that place
PPARγ agonists as one of the most interesting and widely studied anticancer molecules.
Although PPARγ agonists exert significant, antiproliferative and tumoricidal activity in vitro, their
anticancer efficacy in animal models is ambiguous, and their effectiveness in clinical trials in monotherapy
is unsatisfactory. However, due to pleiotropic effects of PPARγ activation in normal and
tumor cells, PPARγ ligands interact with many antitumor treatment modalities and synergistically
potentiate their effectiveness. The most spectacular example is a combination of PPARγ ligands with
tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML). In this setting, PPARγ activation
sensitizes leukemic stem cells, resistant to any previous form of treatment, to targeted therapy.
Thus, this combination is believed to be the first pharmacological therapy able to cure CML patients.
Within the last decade, a significant body of data confirming the benefits of the addition of PPARγ
ligands to various antitumor therapies, including chemotherapy, hormonotherapy, targeted therapy,
and immunotherapy, has been published. Although the majority of these studies have been carried
out in vitro or animal tumor models, a few successful attempts to introduce PPARγ ligands into anticancer
therapy in humans have been recently made. In this review, we aim to summarize shines and
shadows of targeting PPARγ in antitumor therapies.