In contrast to the decline in mortality in other cancers, the incidence of pancreatic ductal adenocarcinoma (PDAC) is increasing, and therapeutic approaches, for the most part, have not been successful at improving survival in patients. Although recent advances in immunotherapy have shown efficacy in various solid cancers, comparable efficacy in PDAC has been limited by a complex tumor microenvironment (TME) that creates an immune suppressive milieu ripe for tumor progression. Thus, bold interventions that can overcome immune barriers in the PDAC TME are urgently needed to reduce the mortality stemming from this recalcitrant disease. The U01 ?Consortium for PDAC Translational Studies on the TME? was created through the National Cancer Moonshot initiative to accelerate the pace of progress in innovative therapies targeting the TME in PDAC, especially those geared towards immune-based modalities. Our proposal is in response to the companion U24 RFA to create a resource center for the five funded Consortium sites, which we call Pancreatic Ductal Adenocarcinoma Translational Resource Center (PATReC). The PATReC will be co-led by Drs. Ignacio Wistuba and Anirban Maitra, two established molecular pathologists at UT MD Anderson Cancer Center (UTMDACC) with long-standing expertise in cancer biomarkers, tissue based molecular profiling, and with respect to one co-leader (AM), specific expertise in PDAC biology, disease models and experimental therapeutics. They will be supported by an exceptional supporting cast, including Drs. Jack Lee (biostatistics), Andy Futreal (cancer genomics and computational biology), Jason Roszik (bioinformatics) and Stan Hamilton (co-leader of the NCI MATCH biorepository). The overall goal is to support the consortium efforts in multiple areas including: providing an administrative infrastructure for coordinated interactions amongst the U01 awardees; facilitating centralized biospecimen banking and distribution; enabling centralized data storage capabilities; and credentialed biostatistics and bioinformatics support with the ultimate goal of designing translationally relevant combination interventions targeting the TME in PDAC.
In Aim 1, we will support administrative coordination amongst the U01 sites by ensuring effective communication, cooperation, and access to rapid data exchange that will advance the goals of the individual Consortium sites. The PATReC will serve as the central ?hub? for virtual and in-person communication across the entire Consortium.
In Aim 2, we will utilize our unique institutional infrastructure to provide centralized data management services that will be readily accessible to all Consortium sites via a secure website, and provide bioinformatics and biostatics services for the analyses and interpretation of data.
In Aim 3, we will standardize bio-banking activities and develop standard operation procedures (SOPs) for biospecimen collection, processing and distribution, as well as provide access to biologically relevant PDAC preclinical resources. We envision that the PATReC will be an indispensable element as we make meaningful progress towards targeting the TME in this lethal disease.
Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer death in the United States with increasing mortality rates making it the deadliest of cancers grouped by organ site. The tumor microenvironment plays a complex role in suppressing host immune function and current immunotherapeutic approaches are mostly unsuccessful. The Pancreatic Ductal Adenocarcinoma Translational Resource Center (PATReC) will support the infrastructure of the proposed U01 Consortium by providing administrative coordination, facilitating centralized biospecimen and data banking and distribution, and extend biostatistics, bioinformatics and pathology expertise relevant to PDAC that will ultimately lead to the design of successful immunotherapy approaches targeting this lethal disease.
| Goggins, Michael G; Lippman, Scott M; Constantinou, Pamela E et al. (2018) Intercepting Pancreatic Cancer: Our Dream Team's Resolve to Stop Pancreatic Cancer. Pancreas 47:1175-1176 |
