Pancreatic cancer
Pancreatic cancer is the fourth leading cause of cancer death in Canada. Most patients present with metastatic disease, do not benefit from surgery, and respond poorly to chemotherapy. Our group, as part of PanCuRx, launched the COMPASS (Comprehensive Molecular Characterization of Advanced Pancreatic Ductal Adenocarcinoma) trial in 2016, which has resulted in the largest international repository of genomes and transcriptomes from late-stage pancreatic cancer. We work in close conjunction with clinicians to understand the evolution of pancreatic cancer through diverse experimental models and high-quality bioinformatics.
Modelling patient tumors
The Notta lab uses human organoid and mouse models to uncover mechanisms of disease evolution and therapeutic resistance in pancreatic cancer. Our collaborations have shown patient-derived organoids in 3-D culture can predict patient responses to chemotherapy (Tiriac et al, 2018). Through a variety of techniques, we investigate tumor biology to improve treatment selection for patients with metastatic pancreatic cancer.
Understanding intra- and inter-tumoral heterogeneity
We previously identified that pancreatic cancer metastases harbor increased levels of KRAS allelic imbalance and whole-genome doubling compared to primary tumors (Notta et al, 2016; Chan-Seng-Yue et al, 2020). Through genomics, transcriptomics, and single-cell techniques, we study the genetic subtypes of this lethal disease, which has contributed to the characterization of homologous recombination deficient (HRD) pancreatic cancers (Golan et al, 2021) and shown poor responses to FOLFIRINOX among the Basal-like transcriptomic subtype (O’Kane et al, 2020).