What's very interesting about the treatment is that it's based on the PPAR-gamma mechanism. Improving on the troglitazone response would involve finding drugs tailored to each cancer that act via the PPAR-gamma pathway. Troglitazone affects the cancers by slipping through the cell into the nucleus, where it hooks onto PPAR-gamma. The receptor, which sits on the DNA, then switches on transcription. The activated PPAR-gamma starts up transcription, expressing genes that order the cell to head towards maturity rather than metastasis.
Untreated cells continue their uncontrolled proliferation.
In 1994, he reported that PPAR-gamma could control fat cell differentiation. Precursor fat cells in connective tissue need the switch to be activated in order to turn into mature fat cells. About a year later, Spiegelman, working with a group at the Salk Institute in La Jolla, Calif., found that troglitazone and similar drugs could turn on PPAR-gamma. The timing could not have been better. Not long afterwards, the FDA approved troglitazone for clinical use in diabetes.