The existence of unresponsive tumors and the appearance of resistant tumors during the
course of treatments both justify that we increase urgently the panel of pharmacological molecules
able to fight cancer. An interesting strategy is drug reprofiling (also known as drug repositioning, drug
repurposing or drug retasking) that consists of identifying and developing new uses for existing drugs.
This review illustrates drug reprofiling with troglitazone (TGZ), a synthetic PPARγ agonist initially
used for the treatment of type II diabetes. The fact that TGZ also displays anticancer effects is known since the end of the
nineties but its development as an anticancer agent was slowed down due to hepatotoxic side effects. Part of the knowledge
available for TGZ, mainly the molecular basis for PPARγ activation, its metabolization pathways and the side effects
on hepatocytes, were taken into account to elaborate new molecules. Key findings were that unsaturated TGZ derivatives,
when compared to TGZ, do not activate PPARγ, exhibit a higher efficiency on cancer cells and a lower toxicity towards
hepatocytes. However, a weakness is that the mechanisms involved in the anticancer effects are still not completely understood
and that the efficiency of such derivatives has not yet been completely studied in vivo. Data about this point
should become available very soon from animal models and this will be a prerequisite to initiate clinical trials with these
potential new anticancer drugs developed from a drug repurposing strategy.