Adrian Levine

Resident Physician, Neuropathology, University of British Columbia, Vancouver General Hospital

Project Entitled: “Improving Precision Medicine for Pediatriac Glioma”

Project Summary:

Brain tumors are the leading cause of cancer mortality in children. Recent precision medicine initiatives have led to improved targeted therapies for many tumors, but there remain ongoing challenges in predicting the drugs to which a given patient will respond. Therapies are generally selected based on a tumor’s DNA mutations, however the presence of a given alteration does not always imply that the corresponding cellular pathway is driving tumor growth. The hypothesis of this project is that integrating gene and protein expression with DNA mutations will be more predictive of response to therapies than the DNA alone. We will create a novel clinical assay using the NanoString technology that measures levels of a customized set of genes and proteins in a single platform. The resulting data will be processed through a novel bioinformatics pipeline, which will integrate the multiplexed output and predict the best treatment options for a given tumor. This test will be validated on a set of clinical cases with known responses to targeted therapies, and subsequently will be licensed to other institutions. The impact will be enhanced treatment of pediatric gliomas and improved understanding of the pathways driving tumor growth.

Impact of Receiving Award

I am honoured to be awarded the Richard Motyka Brain Tumour Research Fellowship because it allows me to pursue a fascinating and exciting project to improve the molecular testing that is used to diagnose pediatric gliomas and identify targeted therapies.

As a medical student and intern rotating through the neurology, neurosurgery, oncology, and pediatrics services, I witnessed the devastating impact that glioblastomas and other brain tumors have on patients and their families. I was motivated to complete a residency in neuropathology to understand the biological drivers underlying the growth of brain tumors, and to develop the diagnostics that guide their management. I am now embarking on this fellowship to further my scientific training at the Hospital for Sick Children under the supervision of Dr. Cynthia Hawkins, one of the leading scientists in the field.

I am immensely grateful to the family of Richard Motyka and to Brain Tumour Foundation of Canada for their generosity in supporting this important research. This is an amazing opportunity to pursue my goal of developing a career as a clinician scientist. I hope that my work will contribute to improving the treatment and survival of glioblastoma patients in the future.
 

Update Report – July 2022

Final Report – March 2024

Pediatric brain tumors have had major advances over the past decade in our (1) understanding of the underlying biology and (2) in developing specific treatments that address the vulnerabilities in a given tumor type. In particular drugs that harness the immune system to fight tumors, as well as those that target specific growth pathways that feed tumor growth, have had major impacts on the survival of some tumors. However, despite the effectiveness of these therapies, we still have challenges identifying the best patients for a given treatment. My project therefore, was to develop two new clinical tests that evaluate (1) the level of immune activation in a tumor biopsy and (2) which cellular pathways are driving tumor growth. We used these tests to profile a large set of pediatric brain tumors and found numerous insights that help us better understand these diseases. In particular we found that knowing the levels of immune cells in a tumor sample can identify patients that are most likely to respond to immune-based therapies and avoid the use (and potentially toxic side effects) of chemotherapy and radiation. We now look forward to implementing these tests in routine clinical use to help more patients going forward and to continue to develop our understanding of the mechanisms that contribute to tumor growth.