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2013/2014 Annual Doctoral and Postgraduate Fellowship Grant Recipients

Shawn Chafe, BC Cancer Agency, Vancouver

Project Title

Targeting breast cancer metastasis and premetastatic niche development through carbonic anhydrase IX inhibition 

Project Overview

Tumours with an inadequate oxygen supply activate the CAIX protein as a survival strategy, which in turn contributes to its aggressiveness. These poorly oxygenated tumours have ways of tricking the body’s immune cells into working for the tumour, instead of against it, by releasing certain chemical signals, and this enhances the ability of the tumour to spread to other parts of the body. Dr. Chafe has discovered that the CAIX protein is involved in the release of certain signals that will actually promote movement of certain immune cells, with the capability of suppressing the body’s natural defence mechanisms to the tumour, to organs where the breast cancer cells are likely to spread.  Dr. Chafe hopes that blocking the function of  the CAIX protein will reduce the movement of these immune suppressive cells and in turn restore normal immune responses against the tumour, which may help to decrease the spread of the tumour and its aggressiveness.

During the second year of funding, Dr. Chafe will extend these findings to human models of metastatic breast cancer to potentially identify additional factors that may be targeted to improve the survival of patients with metastatic breast cancer, as well as to assess whether these factors can be utilized as important indicators of treatment response to the therapeutic strategy of targeting CAIX.

Samantha Grist, University of British Columbia, Vancouver

Samantha Grist.jpgProject Title

3-D tumour models with integrated hypoxia control and measurement for cell-based cancer treatment screening

Project Overview

This project focuses on the development of a platform for the testing of breast cancer treatments that better predicts the response of animal/human models than traditional cell-based drug screening platforms. Potential treatments often fail in later stages of the drug development process; by better predicting the results of these trials in earlier testing stages, this project hopes to help minimize resources wasted on ineffective treatment candidates.

Towards these goals, this project focuses on reproducing two important aspects of the micro-scale environment around breast tumour cells: the three-dimensional (3-D) scaffold on which they grow, and the oxygen levels around them. To reproduce these important aspects outside of the body, the team is developing micro-scale fluidic systems that can reproduce spatial oxygen gradients, critically low oxygen levels, and time-varying oxygen profiles like those that affect the response of human tumours to drugs. They will also integrate materials into the device to provide a 3-D environment for cell growth. By better predicting human responses at early testing stages, the project has the potential to form a highly powerful tool for future cancer research.

The proposed platform could create a valuable tool in cancer treatment testing, bridging the gap between traditional in vitro and in vivo studies to facilitate the identification of ineffective treatments earlier in the testing process. As this would reduce the costs associated with treatment development, such a platform could significantly help cancer researchers in developing new, effective breast cancer treatments.

Tehmina Masud, BC Cancer Research Centre, Vancouver

Project Title

Investigating the roles of clonal transcriptomes and epigenomes in the evolution and treatment of triple-negative breast cancers

Project Overview

This project seeks to investigate how high-risk, aggressive breast cancers evolve as they grow. The Aparicio lab has shown that these cancers are complex with a myriad of gene mutations. As cancers grow, they acquire additional mutations which make tumours drug-resistant. Non-mutational processes may also contribute to tumour progression and drug resistance; these mechanisms are poorly understood. This project will study the non-mutational processes that contribute to tumour evolution and drug resistance, at single-cell level, by grafting human cancer cells into mice. Initially, the team will establish advanced techniques to identify non-mutational aberrations within single tumour cells. Next, the team will examine how these cell populations evolve on exposure to an anti-cancer drug, and identify the most important tumour cell populations associated with drug resistance.

These studies will: (1) determine the role of non-mutational aberrations in cancer evolution and drug resistance; (2) identify new drug targets; and (3) refine tools for patient management.

This study will study the role of epigenetic mechanisms in tumour evolution and drug resistance in triple-negative breast cancer. Additionally, it will lay foundation for improved clinical management of patients.