In cancer research, progress is often marked by new breakthroughs. New drugs, new biomarkers, new understanding of tumour behaviors. But when diagnosed with rare cancers, patients often do not have these breakthroughs to turn to听for hope. Rare cancers involve tumours often defined by scarcity rather than severity, leaving patients with doctors who often cannot provide treatments, clinical trials, or even explanations for their illness.
The Jerry Pelletier Initiative: Diagnostic and Therapeutic Innovations for Rare Cancers seeks to change this. Named in honour of the late Jerry Pelletier, funded through D2R鈥檚 Translational Impact Research program, the initiative brings together a large, multidisciplinary network of scientists and clinicians with a common goal: to better understand rare cancers, transforming knowledge into tangible diagnostic tools and personalized therapies.
The initiative is a massive collaborative effort with Principal Investigators Mark Lathrop and Morag Park, supported by a team of co-investigators and collaborators, each bringing their expertise in different stages and aspects of cancer research. The Jerry Pelletier Initiative is a joint venture between the Goodman Cancer Institute, the Victor Philip Dahdaleh Institute of Genomics Medicine (VPDIGM), Research Institutes of 91丝瓜视频 Affiliated Hospitals, and supporting organizations Oxford Nanopore Technologies and 10x Genomics.
Rare cancers left behind
Cancer therapies have advanced incredibly over the past decades. However, not all patients have reaped the benefits equally. Precision oncology has exploded in recent years, and technologies such as genetic sequencing, tumour modeling, and RNA therapeutics have been able to help identify specific tumour targets, refining patients' treatment plans. Rare cancers, however, present a limitation of data. With fewer cases worldwide, researchers have lacked the biological information needed to identify biomarkers or pathways that could serve as therapeutic targets, and small patient populations means investments in treatments aren't lucrative for pharmaceutical companies. This scarcity has left rare cancer patients out of the precision medicine revolution.
The Jerry Pelletier Initiative aims to reverse that trajectory by using advanced genomics, comprehensive tumour modeling, and RNA-based therapeutic strategies to study rare cancer subtypes at an unprecedented depth. Morag Park, one of the Principal Investigators involved in this project, explains: "This is an opportunity to begin to understand alterations in rare cancers, but also to develop new therapeutic strategies to target those alterations. We are essentially building a precision oncology pipeline for the rare cancers that have been ignored in the past.鈥�
A precision oncology pipeline
The project鈥檚 central innovation is a precision oncology pipeline, designed to catch rare cancer cases the moment they enter the clinic. Park explains that the aim is to create a continuous flow from clinic to research and, eventually, back into the clinic. When a patient presents a rare cancer diagnosis, their tumour will be identified by clinicians, sampled, and sent to researchers to be rapidly sequenced, analyzed, and modeled. Eventually, findings will return to the clinic, with the long-term vision that these insights will ultimately guide future treatment decisions and improve patient care.
The project brings together a suite of cutting-edge research tools to systematically decode and model rare cancers. Tumours undergo long-read genome and transcriptome sequencing, generating a comprehensive map of mutations, structural differences, and specific treatment targets; key information to find therapies for understudied rare cancers. In parallel, the team creates patient-derived models by transferring tumour cells into mice to establish growing xenograft models鈥攍ab-grown versions of a patient鈥檚 tumour鈥攁nd by developing cell lines and 3D in-vitro organoid models, which allow researchers to test treatments safely before applying them in humans.
Prof. Yasser Riazalhosseini, a co-investigator on the project, and the Head of the Cancer Genomics Lab at VPDIGM, oversees the genomic analyses of this project. He adds: 鈥淭he breadth and depth of molecular analyses applied to the project cases are unprecedented and are meant to maximize the opportunity to find actionable information. Each tumour specimen will be examined at DNA, RNA and protein layers, using state-of-the-art technologies, including single-cell and spatial profiling approaches in order to generate full-resolution molecular profiles of the tumour鈥�. By combining molecular profiles with living tumour model experiments, the research team builds a functional pipeline capable of identifying, modelling, and ultimately targeting rare tumours with unprecedented precision.
The clinic plays a key role
On top of the modeling and treatment discovery, one of the initiative鈥檚 defining features is its focus on seamless communication between the clinic and the research team. Because the project involves numerous moving parts working on behalf of a very small patient population, clinicians play a critical role in identifying rare cancer patients, informing them about the initiative, and collecting samples. Keeping these clinicians informed is essential, not only so they can clearly explain the project to patients, but also so research discoveries can eventually flow back into the clinic and help guide treatment decisions.
Part of this communication effort involves sending project representatives to tumour boards, meetings where clinicians review difficult cases, to make sure they know about the initiative and the tumour-characterization tools it can offer. The clinical side faces its own challenges, such as navigating ethics approvals for potential cases, engaging already overextended clinicians, and determining eligibility criteria for such a rare and varied patient population.
Prof. William Foulkes, a co-investigator on the project, has extensive experience working with rare cancers. He explains that these barriers aren鈥檛 just administrative; they directly impact how quickly discoveries can make their way back to the bedside. 鈥淭he first hurdle is ethics approval, and it takes much longer than you think,鈥� he says. 鈥淵ou might imagine we鈥檇 get review and approval within weeks, but in fact it takes several months.鈥� Establishing clear inclusion criteria is equally important 鈥淲e need to know exactly who should be included in this study and who shouldn鈥檛. A patient with a standard breast cancer wouldn鈥檛 benefit, because we already have excellent treatments.鈥�
But once the study is underway, Foulkes expects that patient interest will be strong. 鈥淲e鈥檙e only offering this to people who unfortunately don鈥檛 have many options, so my guess is most patients will be "all in" when they hear about it.鈥� Ultimately, he emphasizes that the communication pipeline exists for a single purpose: making actionable discoveries. 鈥淭he best-case scenario is that we find an unexpected genomic target for which there鈥檚 already a drug, and the clinician agrees it鈥檚 a good potential treatment. If the patient responds, that鈥檚 a real win.鈥�
Collaboration is at the core of progress
The complexity of connecting research, clinic, and patients underscores the need for a collaborative framework where every team member鈥檚 contribution is vital. This collaborative spirit extends to the project鈥檚 structure, with frequent meetings discussing all arms of the project. With 32 co-investigators, collaborators, and postdoctoral researchers involved, the initiative reflects a recognition that no single lab or discipline can tackle rare cancers alone. Park emphasizes this, saying 鈥淚 have built for the last 25 years projects like this with clinicians, with pathologists, with bioinformaticians and these projects never succeed unless you have everybody at the table. Every single person is as important to this project as anybody else. This philosophy was embedded within the project from the start鈥�.
The long-term aim of the Jerry Pelletier Initiative is clear: to build a pipeline that takes rare cancers from being poorly understood to being deeply mapped, targeted, and treatable. The tools developed through this project could ultimately redefine how these diseases are diagnosed and managed. More broadly, the initiative contributes to a vision of an inclusive genomics-driven future for medicine. By focusing on cancers that have been overlooked, the project helps make precision oncology more equitable and more responsive to the full spectrum of patient needs. 鈥淭hese patients fall through the cracks, and as we get better at treating more prevalent cancers, we'll be left with rare cancer patients,"听Park concludes,"That's why this is a really important time to start to work on these cancers and to identify mechanisms or therapeutic opportunities.鈥�
Rare cancers require augmented coordination, communication, and collaboration to overcome the scarcity of data and resources. The Jerry Pelletier Initiative is precisely addressing this challenge, establishing a comprehensive framework to ensure that rare cancer patients receive the attention, research, and potential treatments they need.
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