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Blocking Tumor Growth

The quest to conquer cancer is undoubtedly one of the holy grails for scientists today. An array of research projects, including many at NewYork-Presbyterian Hospital, are devoted to the development of diagnostic tools, medical therapies, surgical techniques, new vaccines, tricks to strengthen the immune system, and other weapons against this formidable enemy.

Scientists now know that the process governing the growth of blood vessels (angiogenesis) plays an important role in the growth of cancerous tumors. Researchers have sought ways to inhibit the process by targeting specific growth factors. Such work has proven a highly promising strategy so far, and is the focus of continued research by Jessica Kandel, MD, Associate Professor of Surgery in the Institute for Cancer Genetics and Director, Charles Edison Laboratory for Pediatric Research.

Eight years ago, Dr. Kandel, Darrell Yamashiro, MD, and colleagues at the Pediatric Tumor Biology Laboratory were the first to describe the way experimental pediatric tumor growth could be suppressed by blocking a molecule called Vascular Endothelial Growth Factor, or VEGF, from performing its natural job. Their laboratory research provided key preclinical data about an antibody to VEGF, which is the basis of the drug now called Avastin. Approved by the FDA in 2004 for adults with colorectal cancer, Avastin is now gaining use in the treatment of lung and breast cancer.

The year 2004 also marked the first phase I trial of Avastin for children with solid tumors, conducted internationally by the Children's Oncology NCI cooperative group under Principal Investigator Julia Glade Bender, MD, Assistant Professor in the Division of Pediatric Oncology. The Phase I trial was completed this September, and paved the way for more widespread evaluation of this new therapy in children with refractory cancers. "Avastin has been shown to extend the lives of adults with metastatic colon cancer, and it is hoped that the same kind of survival advantage will be seen in children," says Dr. Kandel. Phase II studies of Avastin in children will begin later in 2006. "This is a very exciting example of bench to bedside research," she says.

Dr. Kandel's current focus in the laboratory is to understand how tumors adapt to blockade of VEGF. "Avastin is an effective therapy for some time," according to Dr. Kandel. In patients with colon cancer who do not benefit from other treatments, Avastin may extend their lives by an average of two years. "It is not a cure, however. Tumors eventually acquire resistance."

Understanding how tumors adapt to blockade of VEGF may play an important role in the development of therapies for children with resistant cancers such as neuroblastoma, Wilms tumor, and hepatoblastoma. "As a pediatric surgeon and a researcher it's very exciting to see these new biology-based therapies becoming available to children," says Dr. Kandel.

For information about research on pediatric cancer, please visit www.childrensnyp.org/mschony/Cancer-surgery.html or call 212.304.7810.


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