One of the many challenges of creating effective cancer treatments is getting enough medicine to the tumor to kill it. Many treatments are administered intravenously and blood flow inside tumors is often limited at best. In addition, tumors generate a natural outward pressure, which forces anticancer drugs to “swim upstream.” As a result, treatments must be given in large doses to get more medicine to tumors.
However, researchers have developed a peptide (a chain of amino acids) called iRGD that helps co-administered drugs penetrate deeply into tumor tissue. The peptide has been shown to improve treatment efficacy against human breast, prostate and pancreatic cancers in mice, achieving the same therapeutic effect as a normal dose with one-third as much of the drug. Erkki Ruoslahti, M.D., Ph.D., distinguished professor, Kazuki N. Sugahara, M.D., Ph.D., Tambet Teesalu, Ph.D., and fellow researchers at the University of California, Santa Barbara collaborated on this research.
“Drugs generally have difficulty penetrating tumors beyond a few cell diameters from a blood vessel,” says Dr. Ruoslahti. “This leaves some tumor cells with a suboptimal dose, increasing the risk of both recurrence and drug resistance. The iRGD peptide solves this problem by activating a transport system in tumors that distributes co-injected drugs into the entire tumor and increases drug accumulation in the tumor.”
Drs. Kazuki N. Sugahara and Tambet Teesalu believe the results of this study may have far reaching implications for drug delivery and cancer treatment. Because they can co-administer iRGD, there is no need to modify existing drugs, which means existing treatments can be mixed with the peptide and tested right away.
“It used to be that you had to attach the drugs to a peptide or antibody that would take the drug to the tumor,” says Dr. Sugahara. “However, in this study, we found that we could simply inject the drug and the peptide separately. This works because the peptide sort of opens the gate in the blood vessels only in the tumor.”
Any drug or nanoparticle floating in that tumor area when those gates open enters the tumor and penetrates the tissue with the peptide. The lab has already established collaborations with hospitals and hopes to test whether this iRGD peptide and other related peptides work as well in humans as they do in mice.
“In a way, hopes for finding a way to translate this technology are good,” added Dr. Teesalu. “There’s a really good conservation in the critical binding sites between the mouse and human proteins that act as peptide receptors. We predict that this tissue-specific induced vascular leakage and tissue penetration may also be used to deliver drugs to targets other than tumors.”
The research was published on April 8 in the online edition of Science.