- Role of tumor and stroma subtypes in pancreatic cancer
- Study of novel therapeutic targets
- Identification and evaluation of novel therapies
Research SynopsisThe overall goal of the lab is to identify and study novel therapeutic targets for the treatment of pancreatic cancer, a lethal disease with few therapeutic options. Our research therefore centers on target identification through genomic analysis of human tumors -> validation -> drug discovery and finally clinical trials.
Identification of therapeutic targets Efforts to identify parallel aberrant signaling pathways that are critical for tumor progression and metastasis are critical for cancer treatment. Cancers rarely respond to the same therapies. Genomic analyses of actual human tumors may be helpful to identify more selective targets and biomarkers for the identification of pathways or genes that tumors may be “addicted” to. We have used genomic analysis to identify tumor- and stroma-specific subytpes that may explain clinical and biological differences in outcome in patients.
Mechanisms of tumorigenesis and metastasis
A major focus of the lab is to study novel candidate genes and their roles in tumorigenesis and metastasis. One facet of these studies involves the dissection of the complex signaling mechanisms that relate to these candidate genes and their role in tumor growth. A long-term goal of these studies is to use this information for the development of anti-tumor drugs as novel approaches for cancer treatment.
Evaluation of novel therapeutics
One major challenge in selecting targets for drug development, and patients for drug therapies, is the limited predictive value of traditional preclinical models, cell line derived xenografts. Less than 5% of promising therapies reach the clinic. In order to better address and capture the inherent heterogeneity found in tumors and patients, we have established a Patient Derived Xenograft (PDX) Program where we have engrafted actual human tumors into mice from several tumor types. In particular, we have found that pancreatic cancer PDX models recapitulate patient tumors. We have also recharacterized KRAS-driven mouse models of pancreatic cancer which we use for the study of candidate genes and for novel therapeutics. With the increasing recognition that PDX and GEMMs are more accurate predictors of drug response and better models for biomarker and therapeutic discovery, these models are an exciting first step for the translation of our laboratory studies into clinical trials. We have a number of ongoing collaborations for the development of novel anti-tumor therapies and delivery techniques.