ABC2-Funded Research on Glioma Genomics Featured in Science

December 23, 2021

Accelerate Brain Cancer Cure (ABC2)-funded glioma genomic research at the UC San Francisco is published in the December 12, 2021 online edition of Science - one of world’s top scientific journals.

A team led by scientists from UC San Francisco has discovered that recurrent gliomas may have genetic profiles that are markedly different from those of the initial tumors that spawned them, and has shown that these differences are vastly amplified when a commonly used chemotherapy drug is employed to treat the initial tumors.

The new work may prompt a rethinking of targeted approaches to glioma treatment based on genetic profiling of tumors, and also argues for the judicious use of temozolomide (TMZ), the chemotherapy agent most often used in glioma cases, the team said. “Precision medicine is meant to match therapeutic drugs to target driver mutations on a patient-specific basis, and conversely to avoid drugs that are likely to be ineffective or harmful in select patients. Our results fit the latter category of precision medicine,” Joseph F. Costello, PhD, professor and Karen Osney Brownstein Endowed Chair of neurological surgery and co-senior author of the new research with Barry S. Taylor, PhD, assistant professor of epidemiology and biostatistics. “This work holds the potential to really change the way that patients are treated going forward,” said Max Wallace, CEO of ABC2.

“ABC2 funded our project at very critical time when we had initial but not definitive results,” said Costello. “While our findings raise significant concern about the use of TMZ in subsets of low-grade glioma patients because of the risk of malignant transformation induced by mutations from TMZ, not all TMZ treated patients undergo hypermutation and malignant transformation from TMZ. In fact, many do not. Once we have the biomarker for susceptibility to TMZ-hypermutation, the benefits of TMZ can continue to be realized and the potential cost of malignant transformation can be reduced or eliminated.”

The findings on TMZ have prompted the launch of a clinical trial, expected to open at UCSF in early 2014, which will explore the use of a targeted drug to block TMZ's deleterious effects. “The trial was designed, in part, based on the results of our ABC2 funded study of the mutational evolution of low-grade glioma patients with and without adjuvant TMZ treatment,” said Costello.

“This timely work is sure to make the entire cancer research field take notice of the required need to consider individual variation in response to therapy before prescribing even front line chemotherapeutics,” said Dennis Steindler, Joseph J. Bagnor/Shands Professor of Medical Research in the Department of Neurosurgery of the University of Florida College of Medicine and ABC2 science advisor.



Accelerate Brain Cancer Cure (ABC2) is a venture philanthropy 501(c) (3) nonprofit organization that drives cutting-edge research and treatments for brain tumors. Through strategic partnerships with medical research centers, early-stage biotechnology companies and large multi-national pharmaceutical companies, the organization has awarded more than $20 million in brain tumor research funding to highly qualified investigators and physician-scientists from 42 institutions.

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