M.D. Anderson Receives $9.2 Million Grant

The University of Texas M.D. Anderson Cancer Center has been awarded a five-year, $9.2 million grant from the National Cancer Institute for the further study of targeted anti-angiogenesis therapy research - research aimed at inhibiting the growth of blood vessels that nourish cancerous tumors and allow them to grow.

The U54 grant is a cooperative agreement between M.D. Anderson and the NCI that will give a boost to M.D. Anderson’s integrated anti-angiogenic basic science, clinical and non-invasive imaging research. The University of Texas Health Science Center at Houston, California Technical Institute and the University of Western Ontario, as well as Nycommed Amersham Laboratories and Berlex Laboratories Inc., will also collaborate on the research.

Dr. James Abbruzzese, professor and chairman of the Department of Gastrointestinal Medical Oncology, is the grant’s principal investigator, and Dr. Lee Ellis, professor in the Department of Surgical Oncology and associate professor in the Department of Cancer Biology, is the co-principal investigator.

"Receiving this grant puts M.D. Anderson at the forefront of basic science as well as clinical research in angiogenesis and in developing non-invasive strategies for assessing angiogenic drugs in patients," Dr. Ellis says. "It is a prestigious validation of the institution’s anti-angiogenesis program, recognizing that M.D. Anderson has assembled a large multidisciplinary team of scientists and clinicians dedicated to support such novel research."

Tumors need a healthy supply of blood vessels to develop and survive - without this lifeline, cancerous tumors would die. Identifying the mechanisms that promote this process, known as angiogenesis, and developing drugs that inhibit the growth of tumor blood vessels are two key areas of research for the grant.

M.D. Anderson’s grant funds will support four primary angiogenic research projects, including:

• Examination of surrogate markers of angiogenesis and the specific signaling pathways through which the expression of angiogenic proteins are controlled.
• Clinical validation of specific methods for detection of cell death in response to anti-angiogenic therapies.
• Development of techniques to assess the molecular heterogeneity of blood vessels, to better understand the biologic basis for responsiveness or resistance to anti-angiogenic therapies.
• Evaluation of non-invasive imaging methods to assess the effectiveness of anti-angiogenic agents.

Numerous clinical trials, including ongoing research with the anti-angiogenic agent Endostatin, also will be conducted under the grant. M.D. Anderson began the study of Endostatin in Nov. 1999, one of only three institutions in the nation to conduct the early trials. Results of the Phase I clinical trial have shown the anti-angiogenesis drug did no harm to patients and reduced the blood flow to the patients’ tumors.

One aspect of the Phase I Endostatin trial that will carry over to the research funded by the new grant is the utilization of non-invasive imaging. In addition to standard biopsies, patients enrolled in the Endostatin trial had regular computerized tomography and positron emission tomography scans. These diagnostic tests helped researchers determine the biologic activity of the drug through measurement of blood flow and metabolic activity within tumors, and monitor patients’ reactions to the drug.

"M.D. Anderson’s work with Endostatin, in combination with non-invasive imaging, was absolutely critical in terms of being awarded this grant among very tough competition," Dr. Abbruzzese says. "With this experience, we were able to establish the scientific, multidisciplinary and clinical infrastructure and demonstrate to reviewers that conducting this research was something that we are prepared to do as an institution on a much larger scale."

Still, Dr. Abbruzzese says, more research with non-invasive imaging techniques needs to be done to assess the effectiveness of anti-angiogenic agents.

"With these novel therapies, we’re still not quite sure if they are going to cause tumors to shrink in the same way as some of the more traditional chemotherapy drugs do," Dr. Abbruzzese says. "With the grant, we must continue to refine and explore new imaging methods and develop specific strategies to determine within a few weeks or months, whether the drugs are having an effect on the blood supply of the tumor. Our grant proposal outlines a series of projects based on non-invasive techniques such as MRI, CT and PET scans that we hope will offer an alternative to the more-invasive biopsy."

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