Dr. Benjamin Haibe-Kains
, Director of the Bioinformatics and Computational Genomics research unit at the IRCM, is part of the international research team coordinated by Dr. John Stagg from the Centre de recherche du Centre hospitalier de l’Université de Montréal (CRCHUM) that found an enzyme in triple-negative breast cancer that makes patients less responsive to chemotherapy. This important discovery, published by the scientific journal Proceedings of the National Academy of Sciences (PNAS)
, opens the door to new treatments for this particularly aggressive type of cancer.
Triple negative breast cancer accounts for 15 to 20 per cent of all breast cancers and is associated with a poor prognosis and increased risk of metastasis to vital organs. It is characterized by the absence of three key receptors (estrogen receptor, progesterone receptor, and the human epidermal growth factor receptor 2) typically targeted by standard breast cancer treatments. As such, no targeted therapy is currently available for triple negative breast cancer.
Dr. Stagg’s team found that an enzyme, CD73, makes the breast cancer more resistant to chemotherapy treatments using anthracyclines. Dr. Haibe-Kains, a bioinformatics specialist with a particular expertise in breast cancer, analyzed several gene expression databases from over 6,000 breast cancer patients.
“Our analysis first confirmed that high levels or CD73 is associated with triple-negative breast cancer,” explains Dr. Haibe-Kains. “We then investigated the prognostic value of CD73 and discovered that high levels of CD73 are significantly associated to a low probability of survival at 10 years for triple-negative breast cancer patients.”
As anthracycline-based chemotherapy is the standard treatment for triple-negative breast cancer, Dr. Haibe-Kains also studied the relationship between CD73 and anthracycline efficacy. His analysis showed that, in patients treated with preoperative chemotherapy using only anthracycline, high levels of CD73 are strongly associated to a resistance to treatment, characterized by a non-existent or low rate of disappearance of the invasive tumour.
“Bioinformatics is an essential tool to analyze complex biological data and helps us to better understand a disease and predict how it will evolve,” says Dr. Haibe-Kains. “For this study, our analyses allowed us to confirm the clinical relevance of CD73 in triple-negative breast cancer.”
“Our study’s results are quite encouraging because they suggest that therapies specifically designed to block the action of CD73 could make it possible to enhance the beneficial effects of anthracycline-based therapies,” adds Dr. Stagg. “Indeed, our experiments showed that combining standard anthracycline treatment with anti-CD73 therapy prolonged survival by over 50 per cent in vivo
. Human trials of CD73-inhibitors could begin within five years, which is can offer hope for triple-negative breast cancer patients.”
For more information, read the CRCHUM’s news brief
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