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Research Highlights

Promise - Summer 2009


Stand Up To Cancer Empowers ‘Dream Teams’

Gordon Mills, M.D., Ph.D.

A “dream team” from MD Anderson, Harvard University and Memorial Sloan-Kettering Cancer Center will intensify efforts to target a mutated molecular pathway that fuels endometrial, breast and ovarian cancers, thanks to a three-year, $15 million Dream Team grant awarded by Stand Up To Cancer, a program of the Entertainment Industry Foundation.

The grant will fund the study of PI3K, the “most common abnormally activated pathway in all of cancer,” says Gordon Mills, M.D., Ph.D., chair of MD Anderson’s Department of Systems Biology, director of the Kleberg Center for Molecular Markers and a co-leader on the project.

The team will use its combined cell line studies, animal model research and data from Phase I clinical trials to identify potential biomarkers that will indicate whether a drug will work for specific groups of patients. Clinical trials, based at MD Anderson, will test the validity of candidate biomarkers. Mills expects the first Phase II clinical trial, for endometrial cancer, to open within the year.

Another Stand Up To Cancer-funded Dream Team, designed to advance epigenetic cancer therapy, will draw on the expertise of Jean-Pierre Issa, M.D., professor in the Department of Leukemia. Epigenetics involves the biochemical regulation of genes rather than actual damage to or mutation of DNA. Issa and colleagues were instrumental in the development of decitabine, one of the first epigenetic drugs, which turns on genes that have been chemically shut down.

“Our plans are to find markers that can guide individualized epigenetic therapy by identifying patients most likely to respond,” says Issa. “We’ll start in leukemia, primarily at MD Anderson.”

Through a third Dream Team grant, Roy S. Herbst, M.D., Ph.D., professor in the Department of Thoracic/Head and Neck Medical Oncology, leads research through the department’s innovative BATTLE clinical trial. The research focuses on circulating tumor cells in the bloodstream to detect specific mutations in a variety of cancers and predict patients’ responses to treatment.

The BATTLE program relies on tumor biopsies to detect relevant mutations.

“We hope circulating tumor cells will allow us to do the same thing without having to do a biopsy,” Herbst says. “We would be able to conduct continuous sampling with this technology.”

The charitable initiative Stand Up To Cancer raised most of its funds during a telecast in September 2008 on ABC, NBC and CBS. Stand Up To Cancer received 237 Dream Team applications and awarded $73.6 million to five teams in May.

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Study Reports Major Advance in Lung Cancer Treatment

Roy S. Herbst, M.D., Ph.D.

An international Phase III trial has shown that the oral targeted therapy vandetanib, when combined with standard chemotherapy, improves progression-free survival for patients with advanced non-small cell lung cancer. The findings mark the first clinical benefit of combining a small molecule targeted agent and standard chemotherapy for lung cancer. What’s more, researchers report that vandetanib is a dual inhibitor and is the first single agent in lung cancer to target both the epidermal growth factor receptor and the vascular endothelial growth factor receptor.

Roy S. Herbst, M.D., Ph.D., professor in the Department of Thoracic/Head and Neck Medical Oncology at MD Anderson and the study’s international principal investigator, presented the findings at the American Society of Clinical Oncology’s annual meeting in May.

“This study shows that an oral tyrosine kinase inhibitor can be combined with chemotherapy safely and effectively to provide systematic benefit to patients with this life-threatening disease,” says Herbst.
“The study will have immediate clinical implications. Still, we need to build on this research and turn our focus toward better identifying molecular markers involved, with the ultimate goal of personalizing our patients’ care.”

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Vaccine Helps Body Fight Advanced Melanoma

Patrick Hwu, M.D.

Patrick Hwu, M.D., professor and chair of MD Anderson’s Department of Melanoma Medical Oncology and a co-investigator on the study, presented the findings of a large, multi-institutional Phase III clinical trial at the American Society of Clinical Oncology’s annual meeting in May.

During a previous tenure at the National Cancer Institute, Hwu helped develop the peptide vaccine, which activates the body’s cytotoxic T cells to recognize antigens on the surface of the tumor. The T cells then secrete enzymes that poke holes in the tumor cell’s membrane and cause it to disintegrate.

The Phase III randomized trial of the vaccine with interleukin-2 opened more than a decade ago.

“While more follow-up is needed, this study serves as a proof-of-principle for vaccines’ role in melanoma and in cancer therapy overall,” says Hwu. “If we can use the body’s own defense system to attack tumor cells, we can provide a mechanism for ridding the body of cancer without destroying healthy tissue.”

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Metastatic Colorectal Cancer Survival Improves

There’s been a dramatic increase in survival for patients with metastatic colorectal cancer, say researchers at MD Anderson. They credit new chemotherapy and biological agents, combined with surgical advances in liver resection, with increasing the five-year survival rate from 8 percent to 30 percent.

Scott Kopetz, M.D., assistant professor in the Department of Gastrointestinal Medical Oncology, was the corresponding author on the first study in the past 20 years to look at survival rates for metastatic colorectal cancer. Published in the Journal of Clinical Oncology, the retrospective, population-based study of 2,470 newly diagnosed patients at MD Anderson and Mayo Clinic not only found a significant improvement in overall survival, but also demonstrated a degree and rapidity of improvement rarely seen in metastatic cancers, says Kopetz.

“Many of these patients are not necessarily disease-free but are living with their cancer with a high quality of life,” he says. “For some patients, our goal of making metastatic colorectal cancer a chronic condition is closer to becoming a reality.”

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Promise - Summer 2009

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