The PRecision Oncology For Young peopLE (PROFYLE) Program is the first Canadian precision oncology pipeline that generates personalized molecular profiling in a clinically relevant timeframe using standardized tumour molecular profiling analyses. Tumour‐specific therapeutic targets are identified from the results which are translated into recommendations for clinical care thereby having the ability to transform the care of children, adolescent, and young adult (CAYA) patients with ‘hard‐to‐cure’ cancer. PROFYLE has brought together leaders in CAYA cancer research, clinical oncology, genomics/genetics, bioinformaticians, traditional and novel preclinical cancer modeling platforms, proteomics, health economics, health policy and biomedical ethics, and integrates end‐users and patient advocates in every province, to complete the translational research objectives, implement novel treatment strategies, and translate them into durable societal benefits to Canada. The multi‐ institutional, interdisciplinary structure of PROFYLE provides the basis for a unique national consortium with the ability to effect change for access to targeted therapies and clinical trials for all CAYA patients with cancers.

Please visit PROFYLE webpage for more details.

The PROFYLE program was launched in 2017 with a vision to shift the approach to cancer therapy from a ‘one‐size‐fits‐all' approach to a more refined patient‐specific targeted strategy. PROFYLE takes advantage of Canada’s expertise in next generation sequencing (NGS) technologies, a nationalized health care system, and a breadth of research excellence in cancer biology, genetics and clinical care.

The primary objective of PROFYLE is to be able to generate patient tumor‐specific molecular profiling (including tumor and germline panel and whole genome sequencing, and tumoral RNAseq) in a clinically relevant time frame and to integrate sequential biomarker discoveries over the course of treatment. The results would be able to inform nimble recalibration of potential treatment options for children, adolescent, and young adult (CAYA) patients with ‘hard‐to‐cure’ cancer.

PROFYLE has brought together experts and leaders from across Canada in CAYA cancer research, clinical oncology, genomics/genetics, bioinformatics, preclinical modeling, innovative therapeutics, proteomics, health economics, health technology assessment, health policy and biomedical ethics. The program further integrates end‐users and patient advocates from all provinces. In addition, the PROFYLE team has developed collaborative relationships with other researchers, organizations, programs and industry partners locally, nationally and internationally.

Over the past five years, PROFYLE has developed a national consortium, including more than 20 pediatric and adult institutions, and implemented the first national, multi‐institutional precision oncology pipeline for Canadian CAYA patients with refractory, relapsed and metastatic (‘hard‐to‐cure’) cancer. As a result, the program provides access to cutting edge genomic platforms and bioinformatic analysis and positively impacts the lives of young people with hard‐to‐cure cancer no matter where they live in the country. To date, over 1,100 CAYA patients have been enrolled across Canada in PROFYLE and the Canadian legacy projects it has been building on (the Pediatric Personalized Oncogenomics Project (PedsPOG) in Vancouver, Kids Cancer Sequencing Program (KiCS) in Toronto, and Personalized Targeted Therapy in Refractory or Relapsed Cancer in Childhood (TRICEPS/Signature) in Montreal). In addition, PROFYLE has standardized protocols data collection to ensure that clinical data are being collected uniformly across all

sites. The coordination and harmonization of three regional sequencing sites in Toronto, Vancouver, and Montreal, as well as a single process development and clinical data repository coordinating site, in Calgary, has allowed for equitable access to patients across the country.

As mentioned above, the PROFYLE program consists of a national consortium of over 20 centres (Universities, Hospitals and Research Institutes). These centres have multiple functions that they perform as part of the national precision oncology pipeline including but not limited to enrollment, biospecimen collection, biobanking sequencing, bioinformatics and clinical data collection and storage.

The PROFYLE team has access to national cutting‐edge scientific infrastructure and expertise. Drs. Adam Shlien, Steven Jones and Guillaume Bourque lead the PROFYLE sequencing efforts will continue to have access to world class core facilities and laboratory resources at the BC Genome Sciences Centre, The Hospital for Sick Children/SickKids Research Institute, McGill University, Centre Hospitalier Universitaire Sainte‐Justine and the University of Montreal. The sequencing centres that are part of the PROFYLE national precision oncology platform are three of Canada’s major, highest capacity genome sequencing centres: Canada’s Michael Smith Genome Sciences Centre at BC Cancer (Vancouver), the Toronto Centre for Advanced Genomics (TCAG) and the Pediatric Laboratory Medicine Translational Genetics and Molecular Diagnostics Lab at the Hospital for Sick Children (SickKids) (Toronto), and the McGill University Genome Centre, Canadian Centre for Computational Genomics and Genome Quebec Innovation Centre (Montreal). Each of these are directed by internationally acclaimed genome research scientists and provide sequencing services as a part of a national platform, Canada's Genomics Enterprise (CGEn).

David Malkin (PROFYLE Program Director) and Adam Shlien (PROFYLE Genomics and Bioinformatics Node Co‐Lead), on behalf of all investigators in the PROFYLE Consortium