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Mauro Ferrari, Ph.D., a nanomedicine scientist at The University of Texas Health Science Center at Houston and The University of Texas M. D. Anderson Cancer Center, has received a five-year, $7 million Innovator Award from the U.S. Department of Defense (DoD) Breast Cancer Research Program to develop a targeted new delivery system for breast cancer drugs.
If this new approach proves successful, it could increase the efficiency of drug delivery by concentrating more drug at the site of a tumor. A more efficient drug delivery system has the potential to reduce side effects associated with these drugs.
In global competition, Ferrari was the sole recipient of the DoD Breast Cancer Innovator Award for his proposal submitted in 2008, making him the 17th recipient of this unique award in the last eight years. The Innovator Award is offered to support visionary individuals who have demonstrated creativity, innovative work and leadership in any field who will focus their talents on breast cancer.
"Dr. Ferrari is translating advances in nanotechnology into the prevention and treatment of human diseases; that is why we are here," said Larry Kaiser, M.D., president of the UT Health Science Center at Houston. "His work in the area of cancer is particularly promising and Dr. Ferrari's leadership in this collaborative approach is significant."
Right now, when doctors inject a breast cancer drug, only a small percentage reaches malignant cells. The remaining drug circulates through blood vessels and can kill healthy, non-cancerous tissue. Side effects can include fatigue, hair loss and diarrhea.
With conventional chemotherapy, approximately one of every 100,000 drug molecules reaches its intended destination.
Ferrari's proposed solution to this problem is to package these drugs in miniaturized carriers engineered to search out, recognize and release their payload at the site of the tumor. These nanocarriers are about one hundredth the size of a strand of hair and their contents are measured in billionths of a meter (nanometer).
"Dr. Ferrari is developing new ways to deliver treatments to cancer cells without attacking normal tissue," said Capt. E. Melissa Kaime, M.D., director of the DoD Congressionally Directed Medical Research Programs, the funding agency. "Through the Innovator Award, Dr. Ferrari will have the funding and freedom to pursue these novel and visionary approaches toward eradicating breast cancer."
In 2008, an estimated 182,460 women in the United States were diagnosed with cancer breast and approximately 40,480 died.
When prescribing breast cancer drugs, doctors must weigh risks and benefits. If they order too much drug, it could increase side effects for the patient. If doctors fail to administer enough medication, the cancer may continue to grow.
"Improving cancer treatment poses a complex scientific challenge requiring sophisticated, collaborative research expertise across specialties and across institutions," said John Mendelsohn, M.D., president of the UT M. D. Anderson Cancer Center. "The Innovator Award recognizes Dr. Ferrari's leadership in nanotechnology and in cultivating this team-science approach. We are pleased to contribute our expertise in oncology and in nanoparticle production and targeting to his outstanding research program."
Ferrari's lab has begun preliminary work on the nanocarriers, which could be loaded with therapeutics, diagnostics or a combination of both and designed to hone in on the blood vessels that support tumor growth. Once there, the biocompatible nanocarriers would degrade into harmless byproducts and release the medication.
Ferrari's immediate goal is to significantly increase the concentration of a therapeutic drug in a breast cancer tumor in a pre-clinical study.
Getting the nanocarriers through the body's vast circulatory system and to the site of a breast tumor is no easy task, Ferrari said. The nanocarriers must avoid being corrupted by enzymes, swallowed up by the body's immune system and trapped inside blood vessels.
To avoid biological barriers, Ferrari uses a multi-stage delivery system. The first stage goes to the inner wall of a blood vessel near the diseased cells. As the nanocarrier degrades, it releases the second stage - tiny nanoparticles that penetrate the walls of the inner blood vessels and enter the diseased cells. The third stage is then released and it consists of either the medication to kill the tumor cells or the contrasting agents used for quality images, or both.
Ferrari's nanocarriers can be customized to target different breast cancer presentations. They can be designed to release their payloads over a matter of hours or months. Their shapes can be specifically designed to increase the likelihood of reaching the targeted blood vessels that feed tumor cells.
"Dr. Ferrari and his team will develop multiple innovative treatment modalities that are individualized to treat each patient's unique breast cancer tumor, and possibly also prevent the cancer from recurring or metastasizing," Kaime said.
Ferrari's team includes leaders in mathematical design, particle fabrication and pre-clinical testing from the UT Health Science Center and the UT M.D. Anderson Cancer Center.
The team includes patient advocate, Anne Meyn, who was diagnosed with breast cancer in 1989 and knows firsthand what it is like to undergo chemotherapy, as well as surgery. "We have the potential to greatly reduce side effects by putting chemotherapeutic drugs into the intended areas," she said.
Ferrari's collaborating investigators from the UT Health Science Center include: Paolo Decuzzi, Ph.D., associate professor of The University of Texas School of Health Information Sciences at Houston (SHIS); Vittorio Cristini, Ph.D., associate professor of SHIS; Takemi Tanaka, Ph.D., research assistant professor in the NanoMedicine Division; Xuewu Liu, Ph.D., research assistant professor in the NanoMedicine Division; Ennio Tasciotti, Ph.D., research assistant professor in the NanoMedicine Division; and David Gorenstein, Ph.D., deputy director of the Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases.
Collaborating investigators from the UT M. D. Anderson Cancer Center include: Renata Pasqualini, Ph.D., professor of genitourinary medical oncology; Gabriel Lopez-Berestein, M.D., professor of experimental therapeutics; Anil Sood, M.D., professor of gynecologic oncology; Funda Meric-Bernstam, M.D., associate professor of surgical oncology; and Chun Li, Ph.D., professor of experimental diagnostic imaging.
The program's Clinical Breast Cancer Advisory Board is chaired by Gabriel Hortobagyi, M.D., director of the Multidisciplinary Breast Cancer Research Program at the UT M. D. Anderson Cancer Center. Other board members from the UT M. D. Anderson Cancer Center include: Lajos Pusztai, M.D., D.Phil., associate professor of breast medical oncology; Ana Maria Gonzalez-Angulo, M.D., assistant professor of breast medical oncology; Naoto Ueno, M.D., Ph.D., associate professor of breast medical oncology; Meric-Bernstam; and Massimo Cristofanilli, M.D., associate professor of breast medical oncology.
Members of the Overall Advisory Board are: Lee Hartwell, Ph.D., Nobel Laureate and president/director of the Fred Hutchinson Cancer Research Center, Seattle; Robert S. Langer, Sc.D., one of 14 Institute Professors (the highest honor awarded to a faculty member) at the Massachusetts Institute of Technology (MIT) and recipient of the 2006 United States National Medal of Science; and two executives from the UT M. D. Anderson Cancer Center, Mendelsohn and Hortobagyi.
Ferrari is the deputy chairman of the Biomedical Engineering Department at the UT Health Science Center, an inter-institutional venture that also involves the UT M. D. Anderson Cancer Center and The University of Texas at Austin.
He serves as adjunct professor of bioengineering at Rice University, adjunct professor of biochemistry and molecular biology at The University of Texas Medical Branch at Galveston, adjunct professor of mathematics and mechanical engineering at the University of Houston and president of the Alliance for NanoHealth, Houston.
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