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Intercepting aggressive breast cancers early to improve outcomes

A new partnership between the Terry Fox Research Institute (TFRI) and the Canadian Institutes of Health Research (CIHR) will enable a team of multidisciplinary researchers to cover much needed ground to detect high-risk breast cancer earlier and, at the same time, identify new treatments to address this currently incurable disease. 

For the first time, CIHR’s Institute of Cancer Research (ICR) will co-fund one of TFRI’s prestigious New Frontiers Program Project Grants (PPGs) with $1.1 million in matching funding over the next four years. The funds will enable Princess Margaret Cancer Centre scientist Dr. Rama Khokha to spearhead one of two new PPGs announced this year. 

“We are delighted to have ICR as a partner in funding TFRI’s hallmark research program which is renowned for supporting the best cancer team science in the country.  Not only does this funding make a new research program possible, it provides an outstanding team the funding boost needed in an area of increasing importance – early detection of cancer and identifying improved treatments for patients,” said TFRI President and Scientific Director Jim Woodgett.

 “The Institute of Cancer Research at CIHR is delighted to partner with the TFRI on funding this outstanding project, which proposes to discover novel approaches for the early interception of high-risk breast cancer,” said Dr. Fei-Fei Liu, Scientific Director, CIHR – Institute of Cancer Research.  “The results of this innovative research will contribute to a potential prevention strategy for this disease, which will ultimately improve health outcomes not only for Canadians, but for people around the world.”

With total funding of $2.2 million, Dr. Khokha and her team will employ a multi-pronged approach to achieve their goals of intercepting the disease earlier and intervening with treatment options that are less invasive and better tolerated. They hope to develop precision-based primary prevention options.

“Our team is extremely grateful to TFRI and CIHR for their support. The PPG funding helps tie together the work of our team members in a structured program with cohesion and a common goal,” said Dr. Khokha. With deep experience in several areas of biology, the researchers will employ a “momics” approach, directly studying cells from a variety of clinically well-defined high-risk tissues to determine epigenome, transcriptome, proteome, and metabolome profiles.

They’ll work to delineate breast epithelial and cancer precursor heterogeneity, refine metabolic therapeutic targets through functional analysis, defining breast lineage-determinant DNA damage responses and mapping oriented cell division and cellular differentiation, behaviours that are unique to high-risk breast cancer.

“We’ll focus on discovery of earlier interception or prevention options by looking at pathways that go awry and are corrupted early in the tumorigenic process and try to either stop the development of cancer or, once a cancer develops, co-opt those altered mechanisms to treat the patients in a more targeted way,” explains co-investigator and fellow UHN scientist Dr. Shane Harding. Earlier research efforts identified the determinants of mammary cell dynamics and triggered two prevention clinical trials.

Their approach will transform the collective understanding of breast biology and “facilitate its clinical translation to interventional strategies that will benefit patients at high risk of developing advanced, incurable breast cancer,” said Dr. Khokha, acknowledging that early interception is daunting, but not insurmountable.  Individuals at high risk of breast cancer may have a family history of the disease, carry genetic mutations such as BRCA1 and BRCA2, have dense breasts, or an existing predisposition (e.g. Li Fraumeni Syndrome).

“We understand that patients may feel isolated by their disease, but we want them to know that they are not alone. There are teams thinking about this in very focused ways who are committed to making a difference.”