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Annual Report - 2007-2008 - Research

Annual Report - Winter 2009

Momentum in Targeted Cancer Therapy

Making an Indelible Mark
Brain — Virus Kills Haywire Stem Cells
Breast — The Third Test’s the Charm
Ovarian/Breast/Endometrium — Taking a Systems Biology Approach
Experimental Therapeutics — New Treatments Advance Targeted Therapy
Accelerating Cancer Genome Efforts

Making an Indelible Mark

As researchers learn more about genes, proteins and their inherited or acquired abnormalities, they are increasingly able to design therapies specifically targeted to an individual’s genetic make-up. Personalized treatments will allow physicians to provide the safest and most effective therapies to their patients with the best outcomes.

MD Anderson’s commitment to research in this area will be enhanced by expanded facilities. In June 2008, construction began on the Center for Targeted Therapy, part of the multi-center Red and Charline McCombs Institute for the Early Detection and Treatment of Cancer. “By building this facility and filling it with the brightest minds, the best equipment and the spirit of innovation, we expect to make an indelible mark on the emerging field of personalized medicine,” says John Mendelsohn, M.D., president of MD Anderson.
It’s scheduled for occupancy by 2011.

The center will be home to the Translational Chemistry Service, siRNA Screening Service, Molecular Modeling Service and Non-Coding RNA Program — all available to help investigators at MD Anderson with their research endeavors.

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Brain — Virus Kills Haywire Stem Cells

A tailored virus, Delta-24-RGD, destroys brain tumor stem cells that resist other therapies and cause lethal regrowth of cancer after surgery, including in the most aggressive brain tumor, glioblastoma multiforme.
“We have shown first in lab experiments and then in stem cell-derived human brain cancer in mice, that we have a tool that can target and eliminate the cells that drive brain tumors,” says co-senior author Juan Fueyo, M.D., associate professor in the Department of Neuro-Oncology.

Reported in the Sept. 18, 2007, edition of the Journal of the National Cancer Institute.

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Breast — The Third Test’s the Charm

Three genomic tests separately predict the likelihood that a patient’s breast cancer will recur after surgery without additional treatment, as well as its vulnerability to chemotherapy or to hormone therapy. Each predictor is independent of the others, providing unique information to physicians and patients considering treatment options.

“Existing genomic tests for breast cancer provide information about future risk in general, but not the likely benefit of each treatment option separate from a patient’s overall prognosis if no treatment followed surgery. It’s important to independently assess these three variables,” says W. Fraser Symmans, M.D., professor in the Department of Pathology. “We’ve put these three predictors together for the intended purpose of providing all the necessary information for physicians and patients to decide on the best therapy or combination of therapies for breast cancer from a single assay,” says Lajos Pusztai, M.D., Ph.D., associate professor in the Department of Breast Medical Oncology.

Reported September 2007 at the American Society of Clinical Oncology Breat Cancer Symposium.

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Ovarian/Breast/Endometrium — Taking a Systems Biology Approach

Researchers used systems biology to identify the PI3K pathway as a therapeutic target for cancer and have developed multiple collaborations with industry to move PI3K pathway-inhibiting drugs alone and in combination forward to patient care in endometrial, ovarian and breast cancer. They also have developed a number of approaches to identify patients likely to respond to this approach.

“The systems biology method provides a powerful predictor of patients likely to respond to therapeutic targeting of the PI3K pathway,” says Gordon Mills, M.D., Ph.D., chair of the Department of Systems Biology.

Reported in the August 1, 2008, edition of Cancer Research.

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Experimental Therapeutics — New Treatments Advance Targeted Therapy

Two new inhibitor drugs — PX-866 and PX-478 — entered Phase I trials for patients with solid tumors and advanced cancers, respectively, at MD Anderson and other institutions. “The success of these two drugs is twofold,” says Garth Powis, D.Phil., chair of the Department of Experimental Therapeutics and director of the Center for Targeted Therapy. “By attacking the ability of tumors to survive stress induced by low oxygen, chemotherapy or radiation therapy, we have discovered a new way to treat cancer and increase the activity of existing therapies. This method, however, also can be used to personalize therapy by matching the presence of the drug’s molecular target in the patient’s tumor with the drug.”

PX-866 suppresses the PI3 (phosphotidylinositol-3) kinase pathway that, when activated, decreases patient survival because of its resistance to drugs and radiation therapy. PX-866 stops the growth of tumors, and molecular markers have been identified that may help predict which patients show the best response to the drug.

PX-478 blocks HIF-1 (hypoxia-inducible factor 1), which controls tissue response to low oxygen and provides tumors with the ability to create a new blood supply, allowing their survival and growth. PX-478 attacks the ability of these tumors to activate formation of new blood vessels.

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Accelerating Cancer Genome Efforts

MD Anderson has taken a leadership role in obtaining tumors for the Cancer Genome Atlas (TCGA) project in glioma and ovarian and lung cancers. The TCGA is a comprehensive effort to accelerate understanding of the molecular basis of cancer through the application of genome analysis technologies, especially large-scale genome sequencing. The program, sponsored by the National Cancer Institute and the National Human Genome Research Institute, eventually will lead to cancer treatments customized to target genes and gene products that are abnormal in those cancers. Researchers at MD Anderson’s Kleberg Center for Molecular Markers, which is part of the Red and Charline McCombs Institute for the Early Detection and Treatment of Cancer, work with the disease site teams to lead the effort to obtain and investigate tumors.

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