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CIHR Team in Investigating Autophagy Proteins as Molecular Targets for Cancer Treatment

This team project aims to enhance the translation of promising autophagy-related discoveries and therapeutic strategies to treatments that are beneficial for patients with late stage and recurrent / treatment insensitive cancers.

Project Leaders Sharon Gorski , Julian Lum, Marcel Bally, Robert Young, Karen Gelmon
Project Co-Investigators Helene Cote, Keith Humphries, Xiaoyan Jiang, Steven Jones
Project Contacts

For all project related inquires contact:

Stephanie McInnis
Involved Organizations
Funding Agencies
Atg4B and LC3 interacting.

Atg4B (gray) and LC3 interaction model.

Overview

There is a growing recognition that the process of autophagy has important implications for cancer treatment and tumour recurrence. It is now well established that autophagy is induced when tumour cells are exposed to conditions comparable to those found within growing tumours; conditions which mimic regions of low nutrient status and hypoxia. In addition, many anticancer drugs have been shown to induce autophagy. These studies completed using cell-based assays provide compelling evidence demonstrating an autophagic response in cancer cell lines, but little is known about the response in the context of tumours in patients prior to and following treatment. A primary goal of this project is to determine the relevance and scope of autophagy and autophagy alterations in primary specimens of human cancer. Our goals also include investigating the in vivo effects of autophagy inhibition using mouse models and human tumour xenograft models, and developing selective and potent inhibitors of autophagy.

Select Publications

Atg4B active site topography

A close up of the Atg4B active site showing interaction with LC3

  • Bortnik S, Choutka C, Horlings HM, Leung S, Dragowska WH, Bally MB, Gelmon KA, Gorski SM. Identification of breast cancer cell subtypes sensitive to ATG4B inhibition.¬† Oncotarget. 2016 Aug 19. doi: 10.18632/oncotarget.11408. [Epub ahead of print]
  • Klionsky DJ, Abdelmohsen K, Abe A, ...[730 others], Gorski SM, ...[1732 others], Zughaier SM. ¬†Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy. 2016 Jan 2;12(1):1-222.
  • Lebovitz CB, DeVorkin L, Bosc D, Rothe K, Singh J, Bally M, Jiang X, Young RN, Lum JJ, Gorski SM. Precision autophagy: Will the next wave of selective autophagy markers and specific autophagy inhibitors feed clinical pipelines? Autophagy. 2015 Oct 3;11(10):1949-52. ¬†(Meeting report)







Contact Information

For all project related inquires please contact us.

Stephanie McInnis, Project Coordinator
Genome Sciences Centre, BC Cancer Agency
Email: smcinnis@bcgsc.ca
Phone: 604-675-8000 x 7965
Fax: 604-675-8178