Research Update: Clinician-Scientist Award supports development of organoid-based platform to personalize pancreatic cancer treatment

Pancreatic cancer is one of the most difficult cancers to treat, and clinicians often have limited ability to predict which therapies will work best for individual patients. To help address this challenge, Dr. Robert Grant, a medical oncologist and researcher at Princess Margaret Cancer Centre, received a Marathon of Hope Cancer Centres Network (MOHCCN) Clinician-Scientist Award in 2022. 

Through his project, Mapping Pancreatic Cancer Biology to Drug Responses, Dr. Grant sought to better understand why pancreatic cancers respond differently to treatment. His team combined genomic sequencing with patient-derived organoids—laboratory models grown from a patient's tumour—to test how individual cancers respond to different drugs. 

The project helped establish and strengthen a platform for organoid-based drug testing, generating valuable data to explore new approaches to treatment selection for pancreatic cancer. While predicting drug response from genomic data alone proved more challenging than anticipated, the findings helped pave the way for clinical application, leading to the development of standardized workflows and the launch of the ADOPT Phase II clinical trial, which is now enrolling patients. Supported by funding, mentorship, and expertise from the Marathon of Hope Cancer Centres Network, the work has been presented at leading international conferences and has laid the foundation for future precision oncology studies. 

We spoke with Dr. Grant about his research, the progress his team has made, and how organoid-based drug testing could help improve treatment options for pancreatic cancer patients. 

MOHCCN: How would you describe the original objectives of your project to a lay audience? 

Dr. Robert Grant: The project aimed to learn why pancreatic cancers respond differently to treatment and to use that knowledge to guide more precise therapy. We planned to study each patient’s cancer using whole-genome and RNA sequencing and to grow patient-derived organoids, which are small laboratory models of a patient’s tumour. By testing many drugs in these organoids and applying machine-learning methods, we aimed to build a map linking tumour biology to drug response. The longer-term goal was to make treatment selection less empirical and more individualized for people with pancreatic cancer. 

What were you able to achieve through this project? How did funding from the Marathon of Hope Cancer Centres Network help you achieve these goals? 

During the award, we completed the retrospective development cohort work and strengthened the patient-derived organoid drug-testing pipeline, including a multi-point drug screening assay and the statistical framework needed to interpret the results. We also generated the datasets and codebase for the machine-learning analyses, although results show that predicting organoid drug response from genomic data alone is more difficult than anticipated. These lessons led us to a more direct clinical test of the platform: we created standardized patient-derived organoid tumour-board reports and workflows, and opened the ADOPT phase 2 trial, which has now begun enrolling patients. MOHCCN funding supported analytical work that helped enable this clinical translation. 

How are these findings helping to advance precision medicine for cancer? What potential impact could they have on patients? 

These findings aim to help precision medicine move beyond a narrow focus on single genetic changes. The work created a practical path from a patient biopsy to organoid drug testing, multidisciplinary review, and a potential treatment with a drug already approved by Health Canada for another use. The potential impact is to identify additional treatment options for people with pancreatic cancer; whether this improves outcomes is now being tested in ADOPT and related prospective work. 

How has funding from the Network helped advance your career as a clinician-scientist? Has becoming part of the Network helped open new opportunities? 

MOHCCN funding was a milestone in my development as an oncologist treating and studying pancreatic cancer. The award provided support, mentorship, and access to expertise across the Network. The work has generated national and international visibility through presentations at AACR and ASCO and has positioned me to develop future studies in precision oncology.