Bahrambeigi S, et al. Crit Rev Oncog 2019.
Colorectal cancer (CRC) is one of the most common cancers worldwide, and it is considered the fourth most common cause of life-threatening cancers. Diabetes mellitus, especially type 2 diabetes, is an independent risk factor for CRC, due to shared risk factors like physical inactivity and obesity. Thiazolidinediones (TZDs) are among the most common medications for type 2 diabetes mellitus. Recent investigations have suggested a correlation between TZD usage (in a time-dependent manner) and
reduced risk of CRC such that a longer period of TZDs treatment can lead to higher protection against CRC. TZDs have antitumor effects in a wide variety of in vitro and in vivo cancer models through different mechanisms such as the impacts on cell cycle, apoptosis, cell differentiation, and angiogenesis. These effects can be mediated via both peroxisome proliferator-activated receptors γ (PPARγ)-dependent and PPARγ-independent pathways. Due to the protective effects of TZDs in cancer prevention and treatment, they can be considered potent adjuvants in cancer treatment. In the current review, we discuss the effects of TZDs on prevention and treatment of cancers, with special emphasis on CRC and the association of TZD administration with metabolic regulation of T cells in defense against tumor cells.