The overarching scientific goal of the Neurologic Oncology Program is to use a team approach to advance the understanding of brain tumor biology and drive translation into more effective treatments.
The Program does not limit its work to any specific type or group of brain tumors, but rather seeks to apply knowledge gained to the understanding and improved treatment of all grades and types of brain cancers. The Neurologic Oncology Program strives to work collaboratively with other HDFCCC Program with shared interests and includes several individuals whose interests span multiple programs.
The clinical portion of the Program has been successful developing early-phase investigator initiated therapeutic studies and bringing these to the clinic for testing, with particular emphasis on SPORE-related clinical trials. The broad range of publications covering population science, cell signaling, genomics, imaging, and clinical science, as well as the high percentage of intra- and inter-programmatic publications, are the result of a strategically integrated, highly interactive, diverse, and productive Program that continues to make significant progress in reaching its stated goals.
- Theme 1: Improved understanding of the underlying biology of brain tumors
- Theme 2: Predicting patient disease, response, and survival
- Theme 3: Improving the therapy of brain tumors
Theme 1: Improved understanding of the underlying biology of brain tumors
Brain cancer is frequently the result of dysregulation of the processes that govern normal brain development. Understanding neuronal development therefore provides information critical in understanding the origins of glioma. Along these lines, Dam Lim and Arturo Alvarez-Buylla recently showed in a publication in Science that the position of neural stem cells in the developing brain, and their subsequent fate, is governed by a mixed-lineage leukemia 1 (MII1) dependent epigenetic memory system. These studies therefore not only provide insight into brain development but also identify a new pathway that could become dysregulated in cancer. Meningiomas are the most common primary intracranial tumors, but the molecular drivers of meningioma tumorigenesis are poorly understood. Javier Villanueva-Meyer and David Raleigh investigated intratumor heterogeneity in meningiomas to elucidate biologic drivers and reveal new targets for molecular therapy. Using multiplatform molecular profiling of spatially-distinct samples from human meningiomas, in conjunction with the imaging parameter of apparent diffusion coefficient (ADC), they were able to distinguish meningioma regions with proliferating cells enriched for developmental gene expression programs. Another study published by Raleigh and Arie Perry in Cancer Discovery similarly shed light on the underlying biology of meningioma. In this work the authors found that Enhancer landscapes could stratify meningiomas into three distinct groups that in turn helped predict risk of recurrence and reveal previously unknown therapeutic targets. Finally preclinical studies by Sabrina Ronen and Pavithra Viswanath published in Cancer Research showed that glutamate production from either pyruvate or α-ketoglutarate that was detectable using available magnetic resonance spectroscopy (MRSI) techniques, was a metabolic biomarker of response to temozolomide treatment in mutant IDH1 glioma paving the way to translate MRSI-based monitoring of glutamate to patients in the clinic.
Theme 2: Predicting patient disease, response, and survival
Neuroimaging forms the basis for all diagnosis and treatment decisions in neuro-oncology. Although improvements in anatomic MRI have also improved clinical decision-making, there remains a significant need to detect signals of response or progression faster than what can currently be achieved with standard imaging. The UCSF neuroimaging group has made groundbreaking advances in the areas of metabolic and physiological imaging, most recently with 13C MRSI that is able to detect changes in metabolites produced by tumor cells. Metabolic changes may serve as novel biomarkers of response to therapy within molecular subtypes of glioma and could allow clinicians to rapidly assess early response to treatment and more quickly make critical decisions regarding changes in drug therapy. The members of the NE Program have been successful in acquiring NIH support for a project in the UCSF Brain Tumor Specialized Program of Research Excellence (SPORE PI: Berger) led by Chang and Lupo to assess the role of metabolic imaging for glioblastoma. In addition, Chang serves as the contact PI for a P01 (2P01CA118816-11A1) that assesses the imaging biomarkers of molecular subgroups of glioma. An example of work accomplished in this grant is the study published in Scientific Reports by Viswanath and colleagues exploring biomarkers of response to mutant isocitrate dehydrogenase inhibition in low grade glioma. Another study by the members of NE Program published in NeuroOncology that report on different MR signatures that distinguish recurrent tumor and treatment induced effects highlights the collaborative effort of the multiple disciplines of pathology, surgery, neuro-oncology and imaging. Further demonstration of successful collaboration among members of the NE Program is the study published in JAMA Oncology that demonstrated a clear association of maximal extent of surgical resection of contrast enhancing and non-contrast enhancing tumor with survival in patients with glioblastoma.
Theme 3: Improving the therapy of brain tumors
The development of novel therapeutics for the treatment of brain tumors is at the core of the NE Program and is accomplished through the design and conduct of innovative clinical trials, with a focus on primary gliomas. The portfolio includes investigator-initiated, NIH-supported, and industry-sponsored trials. Studies span the multidisciplinary treatment modalities (surgery, chemotherapy and radiation therapy) and involve important imaging and tissue correlative studies. Members of the NE Program have published the results of a Phase I/II study of Sorafenib and Erlotinib in NeuroOncology Advances, as part of the NCI-funded Adult Brain Tumor Consortium, as well as Phase III trials of novel strategies in newly diagnosed and recurrent malignant glioma. These include a study of Vocimagene Amiretrorepvec in Combination with Flucytosine versus standard of care following tumor resection published in JAMA Oncology, and VB-111 combined with bevacizumab vs bevacizumab monotherapy reported in Neuro Oncology.
Roster of Neurologic Oncology Program
For details on membership criteria, please see our membership page.