project

Assessing Tumour Heterogeneity in Space

Understanding the patterns of spatial heterogeneity in early breast cancer, and how these patterns influence the response of cancer to current treatment approaches.

About Our project

We now recognize that many cancers are highly complex mixtures of multiple different sub-populations of cells. This is critical to patient treatment: if only part of the tumour population is removed using current chemotherapy or even targeted therapy, the surviving cells will grow and ultimately the tumour will reappear or spread further leading to treatment failure and death. This heterogeneity within cancers explains, in part, why the majority of current therapeutic approaches for cancer work best when multiple agents (chemotherapies) are combined. However, as we move into an era of targeted therapeutics it becomes critical to understand the complexity of tumours both at diagnosis and over the course of therapy, so that the appropriate therapies can be applied initially, and then modified over the course of therapy to adapt to changes in tumour composition so as to eradicate all remaining cancer cells.

At present, despite extensive evidence supporting the presence of heterogeneity within cancers at diagnosis (in space) and during treatment (in time), the medical community makes limited use of heterogeneity-informed approaches to diagnose and actively manage treatment of cancers. Future adaptive oncology approaches should include measures of tumour heterogeneity so that patients and their treating physicians 1) understand the degree of heterogeneity within tumours at the time of diagnosis, 2) have tools to measure the potential impact of heterogeneity in the context of treatment offered, 3) have the ability to adapt treatment based on knowledge of key cancer drivers with different cell populations and finally 4) can monitor changes in tumour composition over time to adapt treatment and eradicate disease. The “Heterogeneity in Space” project seeks to obtain a detailed understanding of the patterns of spatial heterogeneity in early breast cancer, and how these patterns influence the response of cancer to current treatment approaches.

Overview

Goal

The overall goal is to capture quantifiable spatial proteomic and genomic/methylomic alterations that can be integrated with existing RNA expression, targeted sequencing and response data to identify measures of spatial heterogeneity.

Objectives

Our objectives are to:

  • Use multiplex in situ proteomics to map intra tumour heterogeneity and perform focused RNAseq/DNA targeted sequencing to match in situ tissue markers to specific mutational heterogeneity;

  • Use multiplex in situ proteomics to identify the relationship between clonal heterogeneity and treatment outcome;

  • To develop informatics approaches to map in situ data on clonal heterogeneity with heterogeneity determined by targeted sequencing;

  • Use laser capture/on slide DNA/RNA extraction and targeted sequencing to validate measures of clonal heterogeneity.

Project Impact

Output from this project will inform future trials by providing robust evidence for the impact of heterogeneity within tumours, developing novel diagnostic approaches to assess tumour heterogeneity and ultimately lead to designing adaptive oncology trials to improve patient outcomes for cancer sufferers in Ontario and beyond. 

This project will allow us to (1) study the correlations among spatial heterogeneity at the imaging, proteomics, genomics and transcriptomics levels, allowing us to develop practical, cost-effective strategies for assessing heterogeneity in clinical samples; and (2) relate patterns of early breast cancer heterogeneity to treatment response, setting the stage for a new class of predictive biomarkers.

Collaborate with Us

We welcome collaborations with cancer researchers across Canada and internationally.

Our Team

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Dr. John Bartlett

  • Project Director, OICR
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Dr. Martin Yaffe

  • PI, Sunnybrook Research Institute