Glioblastoma Precision Medicine Program

A Genomic-Based Treatment Program for Glioblastoma

Project Leaders: Annette Molinaro, PhD; David Solomon, MD, PhD; Jennifer Clarke, MD, and Susan Chang, MD

The goal of this project is to develop and populate a searchable database to collect clinical, pathologic, and genomic data from all patients with WHO grade IV glioblastoma (GBM). We seek to establish an actionable database of mutations (identified with the UCSF500 Cancer Panel) and drugs that may counteract the effects of those mutations to improve treatment of GBM.

Publications

Sloan EA et al. (2019) Recurrent non-canonical histone H3 mutations in spinal cord di use gliomas. Acta Neuropathologica 138: 877-881. 

Zhang Y et al. (2018) Implementation of a targeted next-generation sequencing panel for the diagnosis and precision medicine treatment of adult patients with WHO grade IV diffuse gliomas. Neuro-Oncology 20(6): vi158-vi159.

Hadad S, Gupta R, et al (2023). "De novo replication repair deficient glioblastoma, IDH-wildtype" is a distinct glioblastoma subtype in adults that may benefit from immune checkpoint blockade. Acta Neuropathol 147(1):3.

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Pilot Study Testing Feasibility of Individualized Therapy for Recurrent Glioblastoma

Project Leaders: Jennifer Clarke, MD and Susan Chang, MD

The goal of this project is to assess the feasibility, safety, and efficacy of individualized, patient-specific treatment regimens for recurrent GBM. Individualized treatment regimens are formulated on the basis of gene expression data from the UCSF500 Gene Panel, whole genome, and RNA sequencing. Additional aims of this project include the generation of preclinical models to test selected agents to predict patient response, as well as evaluation of hyperpolarized 13C imaging to assess early response to treatment.

Publications

Autry A et al. (2019) Serial characterization of [1-13C]pyruvate metabolism in patients with glioma and the influence of bevacizumab. SNO 2019.

Autry A et al. (2019) Serial characterization of hyperpolarized [1-13C] pyruvate metabolism in the brains of patients with glioma and healthy controls. ISMRM 2019.

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Next Generation CAR T Cells for Glioblastoma

Project Leaders: Wendell Lim, PhD and Hideho Okada, MD, PhD

The goal of this project is to develop next-generation CAR T cell therapies for treatment of GBM, using combinatorial antigen recognition to achieve precision tumor targeting. Upon completion of current preclinical studies, the project will prepare for the first-in-human clinical trial. 

Publications

Watchmaker PB et al. (2018) Sequential two-receptor priming CAR system to overcome heterogeneous antigen expression. SNO 2018.

Watchmaker PB et al. (2019) Sequential two-receptor priming CAR system to overcome heterogeneous antigen expression. SNO 2019.

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Experimental Viral Gene Therapy for Glioblastoma

Project Leaders: Joseph Derisi, PhD and Nicole Paulk, PhD

The goal of this project is to assess the safety and efficacy of a novel adeno-associated virus (AAV) gene therapy that stimulates the host immune system to target glioblastoma cells in preclinical animal models. 

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Mapping Glioblastoma Evolution Under Therapy

Project Leaders: Aaron Diaz, PhD; Joanna Phillips, MD, PhD; and David Solomon, MD, PhD and Susan Chang, MD

The goal of this project is to investigate evolutionary dynamics between primary and recurrent GBM and concomitant changes in infiltrating immune cells, using RNA sequencing and UCSF500 Gene Panel results. This will be the first study to compare GBM biospecimens at both diagnosis and recurrence with a significant sample size.

Publications

Wang L et al. (2019) The phenotypes of proliferating glioblastoma cells reside on a single axis of variation. Cancer Discovery 9(12):1708-1719.

Wang L et al. (2022) A single-cell atlas of glioblastoma evolution under therapy reveals cell-intrinsic and cell-extrinsic therapeutic targets. Nature Cancer 3(12):1534-1552.