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Molecular characterization of transcriptional repressor capicua in GBM

Principal Investigator:
  • Gelareh Zadeh, University Health Network, Princess Margaret, University of Toronto
  • Canadian Cancer Society

Project Overview

Malignant gliomas, including oligodendrogliomas (OD) and glioblastomas (GBM), are currently incurable brain tumours with few effective treatment options. A better understanding of the molecular underpinnings of glioma is required to find new and better treatments. The goal of this study is to investigate the function of a protein that turns off gene activity called Capicua (CIC) as an important component of a cell signalling pathway that is often abnormal in cancer, called the Ras/ERK pathway. CIC is mutated in most OD tumours and lost in GBM tumours. In this project, Dr. Gelareh Zadeh and his team aim to understand how the loss of CIC contributes to malignant gliomas and to determine whether its loss impacts the efficacy of drugs that are routinely used to block the Ras/ERK pathway that have shown disappointing results in the clinic so far.

In this project, the team will examine how CIC becomes abnormally regulated, along with how the Ras/ERK pathway is activated in GBM, with the intent to discover novel targetable pathways aimed at the CIC protein’s role in cancer. Understanding these new aspects of brain cancer biology will help researchers develop new treatments for these hard to treat tumours.