The next targeted therapies
We’re hitting a plateau and facing a gap of several years before the next targeted therapies emerge from pre-clinical and early stage clinical trials, says Mace Rothenberg, M.D., director of the Phase I Drug Development Program at Vanderbilt-Ingram.
“So far we’ve seen agents directed mainly at two molecular targets—the epidermal growth factor receptor and vascular endothelial growth factor,” Rothenberg says. “We’re now seeing the benefits of those drugs in many common cancers, and we’re beginning to understand how best to utilize them. But we have to find new targets in order to make the next leap forward in our treatment.”
He describes the new targets being explored in the Phase I program—proteins like transforming growth factor-beta, insulin-like growth factor receptor 1, src kinase, and toll-like receptor 9.
“From a clinical and translational perspective, these are both the best of times and perhaps the most challenging of times,” Rothenberg says. “It’s great to have these newer agents that are going to be novel and may allow us to make substantial progress in cancers where we haven’t made much progress—like pancreatic cancer.
“But at the same time, they’re being developed in a much more crowded field. It now becomes a challenge to rationally develop combinations that make both biological sense and have the best chances of making an impact on a therapeutic level.”
Investigators will need to rely on “more robust animal models of human cancer,” Rothenberg says, some of which are being developed at Vanderbilt, and on careful testing in patients.
“It’s exciting to be at a place like Vanderbilt where there’s an open dialogue between the clinicians and the basic scientists who have studied these agents in a pre-clinical setting,” he says. “They are able to guide our decisions about what to look for in the tumor tissue and how to measure it.
“And ultimately we rely on cancer patients, who have been very willing to play an active role in our research. They want to help us understand the drugs, the cancer, and the biology better, even when it doesn’t directly benefit them.”