Fat chance for cancer cachexia
With no drugs on the market and a pair of recent Phase III failures in cancer-associated cachexia, companies could be better off turning to the cause of the wasting disease rather than targeting its symptoms. Two independent academic teams have found evidence that browning of white fat is responsible for cachexia in patients with cancer and propose different strategies to block the process.
Last year, GTx Inc.'s enobosarm missed a primary endpoint of improving physical function in a Phase III trial in non-small cell lung cancer (NSCLC), although it met the co-primary endpoint of increasing lean mass. The compound-a selective androgen receptor modulator-is still in testing for cancer. In 2010, Ark Therapeutics Group plc discontinued development of its angiotensin-converting enzyme (ACE) inhibitor, Vitor, after the compound failed in a Phase III trial for cancer-associated cachexia. Both compounds address symptoms by reversing rather than preventing changes that cause the damage.
The new studies, from the Spanish National Cancer Research Centre (CNIO) and Dana-Farber Cancer Institute, provide the first mechanistic links between brown fat activation and cancer cachexia-an association that has been known for over 30 years-and suggest 2 ways to stop the decline.
Jan Nedergaard, a professor of molecular biosciences at Stockholm University, told SciBX that many studies have suggested that brown fat activation could play a role in cancer cachexia.