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Understanding resistance to immunotherapy to improve treatment opportunities and outcomes

Canadian Platform to Investigate Primary and Acquired Resistance to Cancer Immunotherapy (CAN-PIVOT)

Immunotherapy is an innovative type of cancer treatment that harnesses the patient's own immune system to recognize and eliminate cancer cells. In the last decade, the use of immunotherapy has increased exponentially, and it is now applied as the treatment of choice in many different cancer types. This popularity comes from the remarkable results seen in some patients treated with immunotherapy, which can lead to a cure in some cases and significantly prolong patient lives in others.

Despite these encouraging results, unfortunately most patients who receive immunotherapy either do not respond to it (i.e. their tumours exhibit primary resistance to the treatment) or only respond to it for a certain period of time (i.e. their tumours exhibit acquired resistance). Additionally, we don't yet have a good understanding of why or how resistance occurs, nor can we reliably identify patients who are likely to respond to this promising but fickle treatment.

To better understand the factors that influence whether a patient's tumour will respond to immunotherapy, the Marathon of Hope Cancer Centres Network (MOHCCN) is funding a team of researchers in Ontario and British Columbia to generate comprehensive molecular and clinical profiles of patients with either primary or acquired resistance to immunotherapy who are representative of the pan-Canadian population of patients exposed to immunotherapy.

The project is led by Dr. Anna Spreafico, a Clinician Investigator and Medical Oncologist at the Princess Margaret Cancer Centre, University Health Network, who is joined by collaborators at the same institution as well as Dr. Janessa Laskin, Medical Oncologist at BC Cancer, and Dr. Janet Dancey, Director of the Canadian Cancer Trials Group (CCTG).

Patients profiled in the project will be recruited at the Princess Margaret Cancer Centre and via the Personalized OncoGenomics Project at BC Cancer, as well as via clinical trials across Canada administered through the CCTG.

The team will generate whole-genome and transcriptome sequencing (WGTS) data and collect detailed clinical information, such as diagnosis, treatment and response details, from each patient. This data will be contributed to the MOHCCN Gold Cohort, which is on track to become the largest and most complete cancer case resource in Canada and which will help advance precision oncology research beyond this project. They also intend to use other funding sources to generate additional data types, such as imaging of tumour samples, circulating tumour DNA profiling through liquid biopsies, and microbiome profiling.

The team will use this rich dataset to better understand the biology of tumours that are resistant to immunotherapy, which will help inform the development of new therapies that can circumvent this resistance. "Identifying mechanisms of resistance to immunotherapy is a fundamental step to enable the development of more-effective treatments that are able to prevent cancer cells from evading the immune system and make them more sensitive to anticancer therapies,” says Dr. Spreafico.

This information will also help identify factors that predict which patients are most likely to respond to immunotherapy. As Dr. Spreafico explains, "by doing a better job of selecting patients for this treatment, one of the goals of our study is to improve survival and cure rates while simultaneously avoiding potentially life-threatening and/or long-lasting side effects in patients with low chances of response."

By taking a pan-Canadian approach, facilitated in part by the partnership with the CCTG, Dr. Spreafico emphasizes that this project "provides a powerful collaborative platform to advance cancer research and improve care, following Terry Fox's vision of uniting Canadians against cancer.”

CCTG Investigator Dr Anna Spreafico
Dr. Anna Spreafico

Project title: Canadian Platform to Investigate Primary and Acquired Resistance to Cancer Immunotherapy (CAN-PIVOT)

Key researchers:

  • Anna Spreafico (Princess Margaret Cancer Centre, University Health Network) - lead
  • Janessa Laskin (BC Cancer)
  • Janet Dancey (Canadian Cancer Trials Group)
  • Lillian Siu (Princess Margaret Cancer Centre, University Health Network)
  • Phillippe Bedard (Princess Margaret Cancer Centre, University Health Network)