Cancer Drivers and Intrinsic Vulnerabilities
Pancreatic tumors are remarkably diverse, and patients often respond differently to the same treatments. To develop effective and precise therapies, we must understand and control for these differences at a cellular and molecular level.
Our research is a true "bedside-to-bench" effort. We collaborate with our clinical teams to obtain serial blood, tumor samples, and research imaging throughout a patient’s treatment. This allows us to study the tumor's biology as it evolves, and to quickly translate our findings back into the clinic to benefit patients.
A key focus of our research program is to understand the drivers of pancreatic cancer and identify its vulnerabilities for targeted therapies. We also generate patient-derived models, which are used in cells, animal models, and 3D bioprinting, to study these pathways. The ultimate goal is to translate these studies into clinical trials.
Ongoing Research Projects
Our research is focused on the internal signaling pathways and gene regulation within tumors that promote pancreatic cancer growth and survival.
MYC Biology
Dr. Rosalie Sears has a long track record of discoveries in MYC biology. She has shown that the MYC gene is critical for the aggressive spread of pancreatic cancer to the liver. Dr. Patrick Worth is further investigating the importance of MYC in pancreatic cancer recurrence after a patient has had their tumor surgically removed.
Stress-Response Pathways
Dr. Jonathan Brody is leading a program to study the HuR protein, which is an RNA-binding, stress-response protein. By investigating this pathway, he has identified several key targets—including WEE1, IDH1, PARG, and YAP1—and is pursuing them with pre-clinical and translational studies.
BRCA-PANC Consortium
Established by Dr. Jonathan Brody in 2021, the BRCA-PANC Consortium is a shared resource of tumor samples, biospecimens, and clinical data from patients with BRCA 1/2 pancreatic cancer mutations. As these mutations are present in approximately 5% of tumors, this shared resource will accelerate progress by:
- Identifying resistance mechanisms in these patients.
- Pinpointing novel targets and therapeutic agents.
- Establishing multi-site clinical trials to test candidate therapies.
This powerful framework for collaboration can be expanded to other areas of pancreatic cancer research.
Led by Dr. Charles Lopez, the WOO program is a precision oncology clinical and research program. It uses comprehensive molecular and architectural analysis of individual tumors to assess how patients are responding to targeted therapies.
The WOO trial is part of the Serial Measurements of Molecular and Architectural Responses to Therapy (SMMART) program, which is designed to understand tumor heterogeneity and develop targeted therapeutic approaches. Our researchers gain valuable information on therapy-induced tumor evolution, the development of new therapeutics, and resistance mechanisms in pancreatic cancer. Dr. Gordon Mills is the Director of SMMART Trials and Director of Precision Oncology at the Knight Cancer Institute.
Our researchers are exploring a wide range of projects to identify and target the vulnerabilities of pancreatic cancer.
- Developing therapeutic screens on patient-derived samples – Rosalie Sears
- Developing an improved replication stress assay for use in patient samples – Gordon Mills
- Comparative patient-derived models of cancer: Correlation of genomic, transcriptomics, and IHC phenotyping from individual tumor specimens and paired patient- derived models – Rosalie Sears, Lisa Coussens, Emek Demir, & Jonathan Brody
- Nanoparticle imaging and phototherapy in pancreatic cancer – Khashayar Farsad
- Targeting the DNA repair enzyme, poly (ADP-ribose) glycohydrolase (PARG), for the treatment of pancreatic cancer – Jonathan Brody
- Investigating the role of MYC, PIN1, and PP2A in pancreatic cancer progression, metastasis, and therapeutic resistance – Rosalie Sears
- Investigating the mechanistic and therapeutic role of PIN1 in pancreatic diseases – Brett Sheppard & Vidhi Shah
- Developing IHC/IF CLIA validated methods for pathway biomarker analysis and clinical decision support – Lisa Coussens, Koei Chin, Gordon Mills
- Predictive markers for therapeutic response (PRECEPTS) – Emek Demir
- Circulating hybrid cells as a marker of therapeutic response – Melissa Wong