All drugs against cancer share a problem: They penetrate only a few cells in the tumor. Now a team of biologists has identified a molecule that helps cancer treatments deep into tumors, at least in mice. The approach has yet to be tested in people, but if it pans, it will bypass one of the biggest challenges in the field. "This has huge implications for the treatment of cancer," says David Cheresh, a biologist from the tumor and vascular at the University of California (UC), San Diego, who was not involved in the work.
tumors keep drugs away in two ways. first, their vessels are leaky enough to allow drugs inside. and secondly, they have a high hydrostatic pressure. This means that the fluid has tends to flow from tumors, not to them, and that "any drug must swim upstream, if you will," said Erkki Ruoslahti, a cell biologist and tumor at the Institute of medical research Sanford- Burnham in Santa Barbara, California. Last year Ruoslahti and two scientists in his laboratory, Kazuki Sugahara and Tambet Teesalu, reported on a new peptide, a small molecule called iRGD, which seemed to do a good job of getting inside tumors when it was anchored a drug against cancer.
Now the three, along with several colleagues, tested iRGD with a variety of treatments against cancer in mice. The researchers found that administering iRGD and several common drugs against cancer has significantly increased the amount of each drug went into a tumor, between seven and 40 times without the peptide. He also helped to reduce the dose of medication: about a third as much medicine to give necessary to be effective. This is important because toxicity often makes it difficult to administer high doses of chemotherapy that might help. The group focused on human breast, pancreatic, and prostate tumors grafted into mice.
Ruoslahti think iRGD can treat both the tight blood vessels and the high fluid pressure. The peptide apparently handles this first coupling to receptors on the blood vessels of a tumor, it binds to another receptor on tumor cells which controls the permeability of their vasculature. In a paper published last year, researchers demonstrated that iRGD needed to be chemically linked to any cancer therapy decision because it is much harder to develop it as a drug. In the new work, published online today in Science Express, the researchers report that the peptide can simply be given at the same time the drug.
fault drugs from entering the tumor "is a huge problem for cancer in general," especially when the disease occurs in the brain, which is even less accessible, says Zena Werb, a biologist cell at UC San Francisco. Werb warns, however, that "it is early" to say how promising is iRGD. Cheresh emphasizes that one of the risks is that the peptide could cause new metastases by opening the blood vessels of the tumor and helping . cancer cells to slip Yet they agree that, if the safety and efficacy of iRGD pan out, it could revolutionize cancer treatment for patients with all kinds of tumors Ruoslahti pushes forward;. he and his colleagues filed patent applications on the peptide and are now in discussions with pharmaceutical companies about to test in humans.
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