The failure of a pancreatic cancer therapy, announced Wednesday by its maker Amgen, is yet another sign that a once-promising class of cancer treatments has failed to meet expectations. The latest therapy to flop, called ganitumab, is a monoclonal antibody that targets type 1 insulin-like growth factor receptor (IGF-1R). At Amgen, the drug made it all the way to a phase III clinical trial before the company pulled the plug partway through the trial after concluding that the therapy was unlikely to help patients live longer.
IGF-1R was deemed a promising target after researchers made a number of intriguing observations. Circulating levels of the hormone IGF-1 in a person’s blood were linked to a slightly higher risk of cancer. The receptor is often expressed on epithelial cells, the type of cells that turn cancerous, and it promotes cell survival. Finally, in cell cultures and animals, overexpressing the hormone could produce something that looks like cancer, and that would shrink when treated with an IGF-1R blocker.
But in patients, the drugs are “a serial failure,” says Vuk Stambolic, a cancer researcher at Princess Margaret Hospital and the Ontario Cancer Institute in Toronto, Canada. Other trials of this drug target in lung cancer have not worked, and the drugs’ effects in colorectal cancer are also questionable, Stambolic says.
The Achilles’ heel for many prospective cancer drugs is the biology. In short, it usually turns out to be more complicated than first thought. It may not be enough to go after IGF-1R alone, and the patients in these trials have very advanced disease and may be less likely to respond to narrowly targeted treatments. The work in animals and cells also may not fully mimic real life. “I think that the model is probably only partially representative of what happens in cancer,” Stambolic says.
Various companies are also testing a class of drugs that target both IGF-1R and the insulin receptor. The hope is that the double whammy will be more damaging to tumors.