New funding to address chemotherapy resistance in esophageal cancer

RI-MUHC researchers have received $7.5 million from the Canadian Cancer Society and the Canadian Institutes of Health Research for new study to personalize treatments

Esophageal cancer is one of the most aggressive tumours and is the fastest rising cancer in North America. This cancer has a poor prognosis, with a 5-year survival rate of less than 20 per cent. Although treatments such as surgery, chemotherapy, and radiation are frequently used to help cure this tumour, these therapies are difficult for patients and frequently ineffective.

Dr. Lorenzo Ferri is working hard to change outcomes for patients with esophageal cancer. A senior scientist in the Cancer Research Program at the Research institute of the McGill University Health Centre (RI-MUHC) and a professor of Surgery and Oncology at McGill University, Dr. Ferri is lead investigator of a large international team project that has just received five years of funding to improve treatment for esophageal cancer patients.

“About 40 per cent of patients with esophageal cancer have tumours which are resistant to current treatment options right from the start. To further complicate things, for those patients whose tumours initially respond to chemotherapy, approximately half will experience cancer recurrence. Despite this, chemotherapy is still used because we have very limited other options,” says Dr. Ferri, who is also the David S. Mulder Chair of Surgery and Director of the Division of Thoracic and Upper Gastrointestinal Surgery at the McGill University Health Centre.

This bold, paradigm challenging, project will bring together researchers from across Canada and the United States to decipher the mechanisms driving chemotherapy resistance and devise personalized treatment strategies to critically transform the way we treat patients with esophageal cancer.

The researchers will be collecting data and tumour samples from 300 newly diagnosed patients across Canada, prior to and after chemotherapy. They will perform a comprehensive analysis of this tumour tissue using a multi-omic approach, which combines the latest genomics, transcriptomics, proteomics, epigenomics and metabolomics techniques. In addition, they will develop and employ innovative cancer modeling systems, such as organoids and cancer-on-a-chip – techniques that use cell culture to replicate tumour tissue in the lab. These will be used to screen existing approved drugs, alone and in combination with chemotherapy, resulting in unprecedented information about potential treatment options that could be targeted to an individual’s unique tumour. 

“Using these state-of-the-art techniques, we will create “patient avatars” that will be used to determine which treatment works best for a specific tumour in a specific patient, thereby addressing the issue of therapy resistance head on,” explains Dr. Ferri. “By the end of the project, we hope to deliver not only a tool to identify those who will or will not respond to the standard of care treatment, but we also will have a better understanding on how to overcome resistance. Furthermore, using these patient avatars, we will be able to develop a Canada-wide platform for functional precision oncology for patients with esophageal cancer.”

The project brings together several scientists at the RI-MUHC and McGill in Montreal, (co-PI Swneke Bailey, Ioannis Ragoussis, Morag Park, Pierre Olivier Fiset, Nicholas Bertos, Veena Sangwan, Joseph M. Kinsella), as well as researchers from the United States (Sui Huang (Institute of System Biology ), Don Ingber (Harvard), Garry Nolan (Stanford), Paul Mischel (Stanford), Vineet Bafna (San Diego), and Xiaoyang Zhang (Utah)) and leading esophageal cancer surgeons from six Canadian treatment centres (Anna McGuire (University of British Columbia), Stephen Gowing (University of Manitoba), Wael Hanna (McMaster University), Jonathan Yeung (University of Toronto), Andrew Seely (University of Ottawa), and Jonathan Cools-Lartigue (McGill). The project is guided by three committed patient advocates, Teresa Tiano, Jan Almanzor and John Sauter.

From left to right.
​​​​​Front row: Morag Park and Lorenzo Ferri; middle row: Ioannis Ragoussis, Swneke Bailey and Nick Bertos; last row: Joseph M. Kinsella and Pierre Olivier Fiset.
Missing: Jonathan Cools-Lartigue and the collaborators based outside of Montreal.

Titled “Overcoming Therapy Resistance in Gastro-Esophageal Adenocarcinoma - A Trans Canada initiative”, the project is funded by $4.7 million from the Canadian Cancer Society and $2.8 million from the Canadian Institutes of Health Research.

The grant builds on substantial philanthropic support of Dr. Ferri and his team, thanks to generous donors and the Montreal General Hospital Foundation.

To learn more

Official announcement: the Canadian Cancer Society Breakthrough Team Grants: Transforming Low-Survival Cancers 

Project summary and team profile: Tailoring treatments for people with esophageal cancer