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Research Reveals Cancer Drug Effectiveness Substantially Advanced
Date:4/8/2010

Co-administered peptide directs medicines to tumors and deep into tumor tissue, increasing drug efficacy and reducing side effects

Santa Barbara, Calif. (Vocus) April 8, 2010 -- Researchers have shown that a peptide (a chain of amino acids) called iRGD helps co-administered drugs penetrate deeply into tumor tissue. The peptide has been shown to substantially increase 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. In a transformative paper published today in the online edition of the journal Science, Erkki Ruoslahti, M.D., Ph.D., distinguished professor at Sanford-Burnham Medical Research Institute and founding member of the UC Santa Barbara-Sanford|Burnham Center for Nanomedicine, Kazuki N. Sugahara, M.D., Ph.D., Tambet Teesalu, Ph.D., and fellow researchers at the Center for Nanomedicine and the Cancer Center of Santa Barbara, announced this significant advance in cancer therapy.

“Drugs generally have difficulty penetrating tumors beyond a few cell diameters from a blood vessel,” said 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.”

Dr. Ruoslahti showed in the 1980s that a 3 amino-acid peptide motif (RGD—Arginine-Glycine-Aspartic Acid) serves as a highly selective identifier of malignant tissue, bind-ing to unique receptors in the vasculature of cancers. The RGD peptide’s ability to home to tumors has been used to design new compounds for cancer diagnosis and treatment.

The new variant of RGD (iRGD—internalizing RGD) combines the RGD motif with a tissue penetration element called CendR. Like the earlier RGD peptides, iRGD homes to tumors, but exposure of the CendR motif when the iRGD is enzymatically cleaved acti-vates a transport system through tumor blood vessel walls into the tumor core. In a paper published in Cancer Cell late last year, the research team showed that coupling iRGD to anti-cancer drugs allowed them to penetrate deep into tumors, effectively increasing the activity of the drugs.

The research reported in this latest Science paper adds a new and important twist to the story: The researchers made the unanticipated discovery that anti-cancer drugs do not need to be chemically attached to the iRGD peptide for iRGD to boost their efficacy. Simply co-administering iRGD with a drug enhances the drug’s anti-cancer properties. Co-administration could be even more effective at delivering therapeutic agents inside tumors than conjugating the agents with the peptide. This new paradigm means that iRGD has the potential to enhance the efficacy of already approved drugs without creat-ing new chemical entities, which would complicate the path to approval for clinical use.

In addition to being effective against human breast, prostate and pancreatic cancers grown in mice, iRGD can penetrate other tumor types and could possibly be used to treat most, if not all, solid tumors. The iRGD peptide was also shown to enhance the therapeutic effects of multiple types of anti-cancer drugs, including a small molecule drug, a monoclonal antibody and two nanoparticle drugs. Tumors essentially resistant to a particular drug showed good responses when the drug was combined with iRGD, and tumors partially responsive to another drug were eradicated by the combination.

“We are really excited about the potential of iRGD, and I’d like to thank my colleagues, Kazuki Sugahara and Tambet Teesalu in particular, who made this all happen,” said Dr. Ruoslahti. “These results with human tumors in mice are very promising, but we still have to demonstrate the value of iRGD in treating cancers in humans.”

The Science paper “Co-administration of a Tumor-Penetrating Peptide Enhances the
Efficacy of Cancer Drugs” will be available at http://sciencemag.org after 5:00 PM EST

A video interview with Professor Ruoslahti is available at http://vimeo.com/10780518

Animation of the science is available at http://www.sanfordburnham.org/movies/ER_Animation_MOV.mov

A high-resolution image of the illustration is available at http://www.sanfordburnham.org/img/ER_Vers_Three-8.5x11_300ppi.jpg

About Sanford-Burnham Medical Research Institute
Sanford-Burnham Medical Research Institute (formerly Burnham Institute for Medical Research) is dedicated to discovering the fundamental molecular causes of disease and devising the innovative therapies of tomorrow. Sanford-Burnham, with operations in California and Florida, is one of the fastest-growing research institutes in the country. The Institute ranks among the top independent research institutions nationally for NIH grant funding and among the top organizations worldwide for its research impact. From 1999 – 2009, Sanford-Burnham ranked #1 worldwide among all types of organiza-tions in the fields of biology and biochemistry for the impact of its research publica-tions, defined by citations per publication, according to the Institute for Scientific In-formation. According to government statistics, Sanford-Burnham ranks #2 nationally among all organizations in capital efficiency of generating patents, defined by the num-ber of patents issued per grant dollars awarded.

Sanford-Burnham utilizes a unique, collaborative approach to medical research and has established major research programs in cancer, neurodegeneration, diabetes, and infec-tious, inflammatory, and childhood diseases. The Institute is especially known for its world-class capabilities in stem cell research and drug discovery technologies. Sanford-Burnham is a nonprofit public benefit corporation. For more information, please visit www.sanfordburnham.org.

About Engineering and the Sciences at UC Santa Barbara
Engineering and the sciences at UC Santa Barbara are global leaders in bioengineering, nanotechnology, physics, chemical and computational engineering, marine science, ma-terials science, neuroscience, and geography. UCSB boasts five Nobel Laureates (four in sciences and engineering) and one winner of the prestigious international Millennium Technology Prize. Our students, faculty, and staff thrive in a uniquely-successful inter-disciplinary and entrepreneurial culture. Our professors’ research is among the most cited by their peers, evidence of the significance and relevance of their work. For more information, please visit Engineering.ucsb.edu and Science.UCSB.edu.

Media Contacts:
Tony Rairden
UCSB College of Engineering
805-453-0123

Josh Baxt
Sanford-Burnham Medical Research Institute
858-795-5236

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Read the full story at http://www.prweb.com/releases/cancer/drugs/prweb3853724.htm.


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