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CPRIT funds CTRC study on glioblastoma drug resistance

Posted: Tuesday, December 11, 2012

Andrew Brenner, M.D., Ph.D., assistant professor of medicine, notes that the drug Avastin initially starves glioblastomas by stopping the growth of blood vessels that feed oxygen and nutrients to the tumors. However, the tumors fight back by secreting a factor called CXCL12 to fuel regrowth, making them resistent to Avastin.
Andrew Brenner, M.D., Ph.D., assistant professor of medicine, notes that the drug Avastin initially starves glioblastomas by stopping the growth of blood vessels that feed oxygen and nutrients to the tumors. However, the tumors fight back by secreting a factor called CXCL12 to fuel regrowth, making them resistent to Avastin.

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Contact: Elizabeth Allen, 210-450-2020

SAN ANTONIO (Dec. 7, 2012) — Studies of how to overcome drug resistance in deadly central nervous system tumors called glioblastomas will propel forward, thanks to $755,718 from the Cancer Prevention & Research Institute of Texas (CPRIT).

The research is being conducted at the Cancer Therapy & Research Center (CTRC) of The University of Texas Health Science Center at San Antonio.

The grant, announced Dec. 5, will support the efforts of a CTRC and School of Medicine multidisciplinary team with expertise in medical oncology, neurosurgery and radiation oncology.

Principal investigator is Andrew Brenner, M.D., Ph.D., assistant professor of medicine, whose work is supported by the Sandi and Bob Kolitz Chair in Neuro-Oncology Research and the Kolitz Neuro-Oncology Research Fund.

“This grant is an acknowledgment of the extraordinary science going on at the CTRC,” said CTRC Director Ian M. Thompson Jr., M.D. “Perhaps most exciting is that Dr. Brenner and his team are focused on taking these discoveries to the CTRC’s clinics, where they will be the cancer cures of tomorrow.”

Stopping resurgence of glioblastomas
The drug Avastin, federally approved since 2009, stops the growth of blood vessels that feed oxygen and nutrients to glioblastomas. As the level of oxygen drops, however, the tumors fight back by secreting a factor called CXCL12 to fuel regrowth.

“Studies of Avastin have shown that when brain tumors begin growing again, the amount of this factor, CXCL12, is dramatically increased in patients’ blood, suggesting that it has a direct role in tumors resisting Avastin,” Dr. Brenner said. “All glioblastoma patients end up with resistance to Avastin. The CPRIT grant will enable us to conduct studies to determine which molecular target of CXCL12 we can block to prevent that resistance. We could then use this information to develop a novel treatment for glioblastoma.”

Highly malignant tumors
Glioblastomas are tumors that develop from astrocytes — cells that make up the connective tissue of the brain. These cancers are generally highly malignant and can be located anywhere in the brain or spinal cord.

John R. Floyd II, M.D., said that even when glioblastomas are removed and patients receive chemo-radiotherapy, the median survival is only 13.5 months. The CPRIT grant will allow further study of CSCL12 to seek new treatments.
John R. Floyd II, M.D., said that even when glioblastomas are removed and patients receive chemo-radiotherapy, the median survival is only 13.5 months. The CPRIT grant will allow further study of CSCL12 to seek new treatments.

Low survival rate
“Annually there are approximately 25,000 new cases of glioblastoma each year in the United States, with historical one- and five-year survival rates of 29.3 percent and 3.3 percent,” said John R. Floyd II, M.D., assistant professor of neurosurgery in the School of Medicine and a leading collaborator with Dr. Brenner in the glioblastoma research project. “Even with the surgical excision and standard chemo-radiotherapy, the median survival is only 13.5 months. Novel approaches are desperately needed.”

Texas voters approved a constitutional amendment in 2007 establishing CPRIT and authorizing the state to issue $3 billion in bonds to fund groundbreaking cancer research and prevention programs and services in Texas. CPRIT’s goal is to expedite innovation and commercialization in cancer research and to enhance access to evidence-based prevention programs and services throughout the state.

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The Cancer Therapy & Research Center (CTRC) at The University of Texas Health Science Center at San Antonio is one of the elite academic cancer centers in the country to be named a National Cancer Institute (NCI)-designated Cancer Center, and is one of only four in Texas. A leader in developing new drugs to treat cancer, the CTRC Institute for Drug Development (IDD) conducts one of the largest oncology Phase I clinical drug programs in the world, and participates in development of cancer drugs approved by the U.S. Food & Drug Administration. For more information, visit www.ctrc.net.