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Research Highlight | Jul 1, 2018

Project team in Montreal focuses on reducing side-effects, increasing effectiveness of immune therapies for melanoma patients

In recent years, immune therapy has emerged as one of the most promising developments in cancer research. But despite its proven life-saving potential, researchers still struggle to overcome two major challenges regarding its use: harsh side-effects and the fact that it’s only effective in a small subset of the population.

To overcome these challenges, researchers from the TFRI-funded Montreal Cancer Consortium (MCC) are working to shed light on this promising form of cancer treatment, opening the door for it to eventually reach more patients.

“These therapies have produced incredible outcomes for subsets of patients. However, we currently do not have a complete understanding of why some patients respond to them and others do not,” said Dr. Ian Watson (McGill Goodman Cancer Research Centre), who leads an MCC sub-project that focuses on improving on immune therapy for patients with a deadly form of skin cancer known as melanoma.

As part of the sub-project, Dr. Watson and his team are researching how the immune system interacts with melanoma, a disease that has been proven to respond favourably to anti-PD-1 and anti-CTLA-4 checkpoint inhibitor therapies, two cancer-fighting therapies that release the breaks of the immune system allowing it to attack cancer cells and keep them in check. (Editor’s note: Drs. James P. Allison and Tasuku Honjo, who discovered these therapies, were recently award the Nobel Prize in Medicine for their contributions to cancer treatment).

The sub-project team consists of oncologists, surgeons, pathologists and other basic scientists in Montreal who aim to use their combined expertise to tackle four major objectives, including:

  • Validating and identifying new predictive biomarkers and signatures linked to immune therapy response and clinical outcomes for melanoma patients
  • Explaining the mechanistic relationship between biological, tumoral and immunological modulation impacting treatment efficacy
  • Identifying biological, tumoral and immunological features involved in immune therapy-related side-effects
  • Evaluating the effects of targeted therapies on the tumour-intrinsic and peripheral immune landscape of melanoma

“Our main goals for this project are to first develop new tools for clinicians to help them prescribe therapies that are more likely to be effective while limiting the side-effects that are currently associated with immune therapies. And the second, is to devise new strategies to improve checkpoint inhibitor response,” said Dr. Watson.

Why melanoma?

While the incidence and death rates for most cancers in Canada are stabilizing or declining, melanoma rates are increasing. According to the Canadian Cancer Society, an estimated 7,200 cases of melanoma were diagnosed in Canada in 2017, up from 6,500 in 2016.

Immune checkpoint inhibitors work in approximately 50 cent of melanoma cases. Toxicity and adverse events that often require in-patient hospitalization remain problematic, according to Dr. Watson.

The improved outcomes for melanoma patients treated with checkpoint inhibitors compared to patients with other types of cancer provides an important opportunity to gain a better understanding of tumor and immune responses. Being a part of the MCC allows the team to access a larger cohort of patient samples, technologies and expertise, bringing them closer to their goal of improving response rates for patients that are not responding to immune therapy.    

“In total, the MCC will harness the data-power of more than 18,000 cancer patients annually and more than 50 ongoing precision medicine and immunotherapy clinical trials that, at the moment, are not utilized fully for discovery and innovation,” said Dr. Watson. “This project will allow us to learn from approximately 500 new melanoma cases that are seen annually within the MCC.”