All too often cancer treatments are like taking a howitzer to a hunting party. The treatment might get the cancer, but there’s often a lot of collateral damage. That’s why, almost from the beginning of cancer research, the goal has been to find ways of stopping cancer without harming the rest of the body. Not long ago, the main approach was to find drugs that were effective at killing cancer cells without also killing too many normal cells – or as a corollary, finding ways of ameliorating the effect of the toxic cancer drugs on the rest of the body. But with the advent of modern molecular biology – and the technology that made observations at the molecular level possible – efforts have shifted to finding ways of narrowly targeting cancer cells. There are many approaches underway, here’s a recently announced result with great promise.

The key to this research was the discovery of a peptide (a chain of amino acids) called iRGD that has some very important properties: It binds directly to the blood vessels of cancerous tissue, and more importantly, can actually penetrate the outer membrane of cancer cells. This makes iRGD an ideal delivery medium for nanoparticles of anti-cancer drugs.

Led by Erkki Ruoslahti, M.D., Ph.D., distinguished Burnham professor at UCSB, this research was built on Dr. Ruoslahti’s previous discovery of “vascular zip codes,” which showed that blood vessels in different tissues (including diseased tissues) have different signatures. These signatures can be detected and used to dock drugs onto vessels inside the diseased tissue. In addition to homing in on tumor vessels, the new iRGD peptide penetrates them to bind inside the tumor. Previous peptides have been shown to recognize and bind to tumors, but were unable to go beyond the tumor blood vessels.

“This peptide has extraordinary tumor-penetrating properties, and I hope that it will make possible substantial improvements in cancer treatment,” says Dr. Ruoslahti. “In our animal studies, the iRGD peptide has increased the efficacy of a number of anti-cancer drugs without increasing their side effects. If these animal experiments translate into human cancers, we would be able to treat cancer more effectively than before, while greatly reducing the side effects the patient would suffer.”

Iron oxide nanoworms, which can be visualized by magnetic resonance imaging, were coupled to the peptide and shown to penetrate the tumors, whereas uncoupled nanoworms could not. This demonstrates that iRGD can deliver diagnostics to tumors. The anti-cancer drug Abraxane was also shown to target, penetrate and spread more within tumor tissue when coupled to iRGD than with other formulations.

[Source: Burnam Institute]

Some experimenting with iRGD and animals has taken place, but it should be emphasized that this is a very early phase of testing. Many other cancer drugs and other combinations of iRGD will be on the docket for research. The road to testing and use with humans is still a long journey.