Projects

Project 1: Employing CD11b-Agonists to Render PDAC Responsive to Immunotherapy

David DeNardo, PhD and Patrick Grierson, MD

Project 1 of the Pancreatic Cancer SPORE seeks to understand if targeting integrins on myeloid cells can impact therapeutic responsiveness to immunotherapy in pancreatic cancer. They include studies clinically testing an integrin agonist in PDAC patients and correlative and laboratory studies to understand mechanism of resistance.

Project 2: Mechanisms of Resistance to Neoantigen Vaccines to PDAC

William Hawkins, MD and Robert Schreiber, PhD.

Project 2 of the Pancreatic Cancer SPORE at Washington University plans to use a novel class of optimized neoantigen synthetic long peptide (SLP) vaccines to induce immune responses against class II antigens in pancreatic cancer. Cancer neoantigens have been identified by us and others as important targets of cancer immunotherapy, including immune checkpoint inhibitors (ICI), adoptive cell therapy, and vaccine therapy. Our initial clinical experience targeting neoantigens in pancreatic cancer confirmed that neoantigen DNA and synthetic long peptide vaccines are capable of generating neoantigen-specific T-cell responses in patients. With support from our previous Pancreatic Cancer SPORE and Stand Up to Cancer, we have been testing the safety and immunogenicity of pancreatic cancer neoantigen DNA vaccines (NCT03122106) and synthetic long peptide vaccines (NCT03956056) following surgery and adjuvant therapy. These clinical trials are providing insights into the most effective neoantigen vaccine platform (DNA vs. synthetic long peptide), Preliminary analyses confirm that both neoantigen vaccine platforms can induce robust immune responses to PDAC neoantigens, and suggest that PDAC patients treated with neoantigen vaccines have better than predicted clinical outcomes.

Project 3: Targeting Stress-Induced MK2 as Novel Strategy in Pancreatic Cancer

Kian Lim, MD and Gregory Beatty, MD, PhD.

Project 3 proposes to conduct a phase 1 clinical trial combining a novel MK2 inhibitor ATI-450 with FOLFIRINOX chemotherapy for patients with metastatic pancreatic cancer and to develop a novel immunotherapeutic strategy that can be tested in the future.

SPORE Shared Resources (Cores)

Administrative Core

Directors: David DeNardo, PhD, Ryan Fields, MD, FACS and William Hawkins, MD, FACS

Our Pancreatic Cancer SPORE brings together a diverse group of talented investigators committed to understanding and treating pancreatic ductal adenocarcinoma. The goal of the Administrative Core is to provide executive oversight and administrative support for all of the Pancreatic Cancer SPORE projects and cores. The Administrative Core facilitates communication among the component activities of the SPORE, serves as the home for pancreatic cancer advocate activities, and provides an organizational portal for collaborations outside the SPORE. The Administrative Core also monitors the activities of all program components, ensures compliance with local and federal grant administration guidelines, and facilitates communication and collaboration among program members.

The specific goals of the Administrative Core are outlined below:

• Facilitate intra- and inter-SPORE communication and collaboration including development and maintenance of this website to provide real-time progress updates and contact information. In addition, the core plans and executes bi-monthly working group meetings, monthly Steering Committee meetings, and an annual retreat to facilitate the exchange of ideas and the use of shared resources.
• Provide administrative and fiscal oversight and support for all SPORE components. The Administrative Core interacts with Washington University’s Grants and Contracts Office and the National Cancer Institute staff to prepare and submit annual progress reports and complete other projects as needed.
• Coordinates all SPORE-related meetings. The Administrative Core coordinates the External Advisory Board and Internal Advisory Board meetings, attendance at the annual SPORE workshop, and monthly SPORE Steering Committee meetings.
• Coordinates SPORE Developmental Research Program administrative activities through soliciting and coordinating the review of pilot project applications.
• Coordinates the SPORE Career Enhancement Program. The Administrative Core assists with recruiting and monitoring candidates and awardees in this program.
• Assists investigators with preparing scholarly presentations, publications, regulatory documents and all other SPORE-related products.
• Enhances participation of underrepresented minorities in all SPORE activities.
• Ensures that advocacy issues are properly addressed and included in all aspects of research with patient participants.

The Administrative Core is a shared resource within the pancreatic cancer SPORE and will provide the necessary administrative support for the translational projects and cores.

Biospecimen Core

Directors: Ryan Fields, MD and Mark Watson, MD, PhD

The controlled collection and processing of clinical specimens from patients with PDAC is a critical activity for an efficient and comprehensive program in translational research in the Pancreatic Cancer SPORE. Accordingly, the Biospecimen Core has one overarching aim: We will collect, store, process and distribute biospecimens from all patients with a diagnosis of PDAC seen at this institution to facilitate biospecimen-based translational research.

Our investigators collect malignant cell populations from tumors (from pre-surgical and surgical biopsies) along with normal pancreas, pre-malignant pancreatic lesions and peripheral blood from PDAC patients. Serum and plasma are collected for correlative and future studies. Specimens are collected throughout each patient’s disease course (initial presentation, pre-treatment, post-treatment/follow-up), and, where appropriate, archival specimens from previous biopsies/etc. are retrieved. Specimens are processed to cellular RNA, genomic DNA, whole genome amplified DNA and protein extracts as required for each study. Cellular populations can also be frozen or immediately processed for patient-derived xenograft and/or cell line derivitization/creation.  A tissue microarray (TMA) has been created and will be expanded, creating an important resource for future studies. Importantly, all specimens used for research are extensively and accurately annotated with clinical (pre-treatment, treatment and follow-up) data utilizing the bioinformatics infrastructure at our institution. Expert pathologic review from a dedicated GI pathologist will ensure high-quality annotation.

The aims of the Biospecimen Core are accomplished by expanding the scope of a well-established Cancer Center Tumor Bank and an on-going, funded effort to collect solid gastrointestinal malignancies at our institution.  Specifically, the Biospecimen Core will expand the number of PDAC patients from whom biospecimens will be collected, and serve as a conduit (through data and specimen sharing) to allow for a broader variety of translational research studies in PDAC malignancies, using new and previously banked biospecimens.

The Biospecimen Core is responsible for the identification, enrollment and collection of specimens from adult patients referred to the Siteman Cancer Center (SCC) with newly diagnosed PDAC.  The pathologic material from these patients will be banked utilizing our existing collaboration with the SCC Tissue Procurement Core, drawing on caTissue and other informatics resources developed by the Center for Biomedical Informatics. Clinical data will be annotated and prospectively maintained in a robust clinical database. The Biospecimen Core is integrated with and extends the success of our existing Solid Tumor Tissue Bank and Registry, which was established by the Biospecimen Core (PI Fields) in 2011, to serve as a platform for the investigation of solid tumor pathogenesis.

Available Resources: Tissue MicroArrays (TMAs) Pancreatic Tumors Bloods Animal Models Please contact Jacqueline Mudd for specimen requests at 314-362-2678 or [email protected] with the completed biospecimen request form. Request Form for Biospecimens *Please note requests are honored through a peer-review process.

Biostatistics Core

Director: Esther Lu, PhD  and Malachi Griffith, PhD

The Biostatistics Core provides the statistical design, data management and computational support for all Pancreatic Cancer SPORE investigators and projects. The Biostatistics Core staff will support consultation and collaboration on all aspects of study design, database development and quality control, and analysis, interpretation and presentation of data. The statisticians, epidemiologist and the database manager participating in the Biostatistics Core have a strong record of collaboration, and have been specifically chosen for their broad range of expertise in and experience with clinical trials, laboratory experiments, genetics and genomics research, and epidemiology studies. Our members have participated regularly in planning meetings in which the scientific goals and research methods of the SPORE projects were discussed.

The specific aims of the Biostatistics Core are to provide statistical input to the pancreatic cancer SPORE and, by so doing, to ensure a strong collaborative process. The Biostatistics Core will promote interaction among the projects and pilot studies. Through participation in specific projects and leadership activities, the interrelationships and synergy with the investigator team will accelerate the acquisition of knowledge beyond that which would be expected if these projects were implemented individually, or with research teams that were not interdisciplinary.

The Biostatistics Core has the following specific aims:

• Provide ready access to statistical expertise and computing consultation to the Pancreatic Cancer SPORE.
• Provide biostatistical/epidemiological expertise for the planning, analysis and reporting of laboratory experiments, epidemiology studies, and clinical trials and links to the bioinformatics core resources for microarray data and high-throughput genomics data processing as needed.
• Advise and support pancreatic cancer SPORE investigators and their data collectors (technicians, nurses, data managers, etc.) in the areas of data form design, data collection, record abstraction, computerization, database designing and management, and data quality control.
• Provide the scientific computing expertise required to meet the data management and analytical needs of pancreatic cancer SPORE investigators, and support interpretation and presentation of data.

The Biostatistics Core provides Pancreatic Cancer SPORE investigators with the ability to design and analyze studies that can then be linked to Shared Resources from the Siteman Cancer Center, Clinical Trials Office, Bioinformatics Solutions, and Genome Technology Access Center.  These resources can be leveraged for data form creation and uniform adverse event reporting, Tissue Procurement for sample storage and management (caTissue and related informatics), output from high-throughput genomic assays, and the expertise, tools, and analytic pipelines to streamline analyses and interpretation. The Biostatistics Core supports studies across the entire spectrum, from basic research to clinical translational trials.

Career Enhancement Program (CEP)

Directors: William Gillanders, MD, Robert Schreiber PhD and William Hawkins, MD, FACS

Program Application Information

The Pancreatic Cancer SPORE will fund one to two investigators per year for the life of the SPORE. The 2023 deadline for applications was September 1, 2023 and is now closed. The award will be up to $75,000 per year for up to two years and began on October 1, 2023. Upcoming release date for 2024 will be announced in early May 2024. Applications and instructions will be forthcoming.

SPORE CEP Overview

The Career Enhancement Program is a joint venture between the Pancreatic Cancer SPORE, Washington University School of Medicine (WUSM), and Siteman Cancer Center (SCC). The primary objective of the Career Enhancement Program is to enhance pancreatic cancer research by providing financial support and mentoring for investigators who are new to the field to help build translational research careers in pancreatic cancer. The research initiatives that will be funded by the Career Enhancement Program are expected to have a major translational component, focusing on etiology, prevention, diagnosis, early detection, treatment or population science in pancreatic cancer. The Career Enhance Program’s goals are as follows:

• Recruit and support new investigators to the field of pancreatic cancer research. The Career Enhancement Program is able to support a maximum of two investigators per year. Each investigator will be supported for up to two years, and the money can be used for salary support, laboratory supplies or tuition. The Career Enhancement Program will support both new investigators and established faculty members who are new to the field of pancreatic cancer research.
• Provide mentoring to junior faculty members. Truly successful Career Enhancement Program awardees will be those who subsequently apply for and receive independent external funding to support their pancreatic cancer research careers. The Career Enhancement Program will foster this success by mentoring junior faculty members one-on-one, providing numerous opportunities for research training and didactic instruction, and assisting in the development and review of grant applications.
• Promote participation of women and under-represented minorities in pancreatic cancer research. The Career Enhancement Program will specifically seek to increase the diversity of those participating in pancreatic cancer research through numerous outreach, recruitment, training and retention activities.

The Career Enhancement Program will select awardees from the collaborating SPORE institutions and from other appropriately qualified institutions. Financial support (salary, research supplies and tuition) will be provided for awardees for up to two years. The Career Enhancement Program will facilitate interactions between awardees and all members of the SPORE, emphasizing the basic and clinical science cross-fertilization that is essential to translational research. The SCC, WUSM, and our collaborating SPORE institutions provide outstanding opportunities for career development in translational pancreatic cancer research. We have the broad research base, existing and continually evolving new collaborations, basic science and clinical programs in pancreatic cancer that make the Career Enhancement Program a success. We have established intra-SPORE collaborations with the University of North Carolina, University of Rochester and Johns Hopkins University, broadening the Career Enhancement Program applicant pool and helping to match the interests of junior investigators with local expertise and need. The Career Enhancement Program will be open to all institutions participating in the SPORE.

CEP Past Awardee’s

The CEP has funded a total of four projects.  These projects have led to two clinical trials in pancreatic cancer.  CEP-funded investigators have published in top-tier journals, including Cancer Discover, Clinical Cancer Research, and Cancer Immunology Research. Thus, our CEP investments, in combination with our DRP awards, account for three out of four of the projects in this SPORE renewal application and a significant number of new trials for pancreatic ductal adenocarcinoma (PDAC) patients. These metrics highlight the quality of our applicants and the projects we foster with the developmental mechanisms. We aim to continue our success in this area. A summary of our CEP awardees and their collaborative, high-impact productivity is provided below.

2020 Awardee

Patrick Grierson, MD, PhD

Evaluation of MK2 as a novel Immunomodulatory Target in Pancreatic Cancer. 

Evaluation of MK2 as a novel Immunomodulatory Target in Pancreatic Cancer.  Pancreatic cancer remains among the deadliest cancers, and is presently unresponsive to targeted or immunotherapies, leaving combination chemotherapies as the primary treatment for advanced disease. However, treatment responses to chemotherapy are neither universal nor durable, largely due to intrinsic signaling events that drive resistance as well as a protective extrinsic tumor microenvironment that limits the delivery of chemotherapy and neutralizes anti-tumor immunity.  In preclinical models, near-complete stromal depletion reverts pancreatic cancer cells into a primitive and more aggressive tumor type and clinically, stromal depletion via addition of hyaluronidase fails to potentiate chemotherapy and may increase toxicity. These findings underscore the need to identify novel therapeutic targets in pancreatic cancer.  Grierson has found that adaptive activation of the MK2/Hsp27 pathway is a novel and major resistance mechanism to genotoxic stress in pancreatic cancer, and that treatment with a novel oral MK2 inhibitor concurrent with chemotherapy greatly augments the efficacy of chemotherapy in preclinical models. Furthermore, targeting MK2 causes marked reduction in stromal density and shifts tumor-infiltrating T cells and myeloid cells to an activated anti-tumor phenotype.  Beyond the CEP award, his work has also led to grant support from the Emerson Collective Cancer Research Fund to further study pancreatic cancer.  Dr. Grierson is currently developing a new clinical trial based on this work.

2023 Awardees

“Stromal Reprogramming to enhance MAPK inhibition”

Around 90% of pancreatic cancer cases carry KRAS mutation. Targeting the RAS/MAPK signaling is a promising strategy, although MAPK inhibitors quickly acquire resistance in clinical trials. We hypothesize that reprogramming the tumor microenvironment (TME) will overcome RAS/MAPK resistance and improve standard therapy efficiency.

“Radiation Induced TIP1 as a ADCC Target”

In recent years, the emergence of precision medicine and targeted therapies have revolutionized the landscape of cancer therapy. Among these promising approaches, antibody-drug conjugates (ADCs) have received significant attention due to their ability to selectively deliver cytotoxic payloads to cancer cells while minimizing damage to healthy tissues. ADCs offer the potential to enhance the therapeutic index of potent agents, such as radiation, by precisely directing their delivery to cancer cells expressing specific antigens. The proposed studies will evaluate ADCs that target overexpressed cancer antigens.

“Distinguishing microenvironments restricting and promoting neoplastic transformation”

The advancement of PDAC from preneoplastic lesions will differ based on genomic underpinnings, transcriptional signature, and spatial context. We hypothesize immune cells, including cancer-associated fibroblasts, functionally restrict precursor lesions and acquired genomic alterations within neoplastic cells modify cell-cell interactions that facilitates PDAC development. To evaluate this hypothesis, we will perform single-cell RNA sequencing, DNA sequencing and spatial transcriptomics to evaluate the transcriptional diversity and transitionary states of preneoplastic cells along with the spatial context of each lesion to explore tumor microenvironment (TME) related interactions surrounding each lesion. Defining genomic alterations and changes to the TME for each type of neoplastic lesion will inform the discovery of novel markers that will aid early detection strategies.

Developmental Research Program

Directors: Ryan Fields, MD and David DeNardo, PhD

Program Application Information

The Pancreatic Cancer SPORE will fund up to three investigators per year in the Developmental Research Program. The 2023 deadline for applications was September 1, 2023 and is now closed.  The award will be up to $75,000 for one year (October 1, 2023 through June 30, 2024). Upcoming release date for 2024 will be announced in early May 2024.. Applications and instructions will be forthcoming.

SPORE DRP Overview

The goal of the Pancreatic Cancer SPORE’s Developmental Research Program is to recruit and support developmental research projects in pancreatic cancer, for future incorporation as full SPORE projects or as the basis for applications for other major peer-reviewed funding. The types of research projects to be supported include basic research, clinical research, epidemiological studies, and cancer prevention and control in pancreatic cancer. Projects will expand the scope of translational research and increase the number of investigators committed to pancreatic cancer research. The Developmental Research Program is responsible for recruiting research projects that will promote pancreatic cancer research to help define the new treatment directions and to support early-stage pancreatic cancer research projects so that they may achieve independent funding through competitive applications including R01, SPORE, foundations and other mechanisms. This program is open to all of the institutions participating in the SPORE, and any of their collaborators to maximize the number of innovative and high-quality projects. In addition, plans call for development of new projects with other SPOREs. This program, along with the Career Enhancement Program, is consistent with the Siteman Cancer Center’s overall commitment to the recruitment of minority and underrepresented investigators. New research projects are solicited and funded through developmental funds. Two to three developmental projects will be funded each year throughout the life of the SPORE. Requests for Applications for developmental projects in pancreatic cancer research will be requested annually. All developmental project applications will be reviewed by a Research Development Advisory Committee consisting of scientists (representing basic and applied science) with expertise in pancreatic cancer, a biostatistician, a patient advocate and ad hoc members, as necessary (special expertise, no conflict of interest). This committee will make recommendations to the Pancreatic Cancer SPORE Steering Committee, which will make final funding decisions.

DRP Past and Current Awardee’s

The DRP has funded a total of 10 projects to-date. Our DRP-funded investigators have published their research in high-impact journals including Nature Medicine, Cancer Cell, and Nature Communications. Additionally, research funded through the DRP has led to the development of multiple new clinical trials for patients with pancreatic cancer. A summary of our DRP awardees and their collaborative, high-impact work is provided below.

2023 Awardees

“CCR2 targeted CuNCs-ECL1i-GEM is a novel cancer nanotheranostic”

To date, combination chemotherapy remains the mainstay treatment of PDAC, but treatment response is neither universal nor durable. PDAC cells are intrinsically very resistant to chemotherapeutics. To overcome these barriers, we developed a novel therapeutic strategy through targeting the C-C motif chemokine ligand 2 (CCL2)/ C-C chemokine receptor type 2 (CCR2) axis, a well-established pro-tumorigenic signaling cascade in PDAC. In this project, we hypothesize that CCR2 targeted CuNCs-ECL1i-GEM is a novel cancer nanotheranostic with robust immunomodulatory effect which will potentiate chemotherapy and checkpoint immunotherapy in PDAC.

Clinical Trials in Pancreas Cancer

Clinical trials are research studies that provide hope for patients with cancer. These trials give patients access to new treatment therapies including new drugs or new ways to use existing drugs. They also include new radiation therapies, new surgical procedures, and new ways to combine different cancer treatments.
The ultimate goal of each clinical trial is to find new and improved ways to safely and effectively treat cancer. Clinical trials are important to patients because they give access to treatment that would not be provided otherwise. In addition, they are important because they help get drugs approved and more easily accessible for future patients.
If you are interested in learning more about the Pancreatic Cancer SPORE clinical trials, you should ask your doctor or nurse if a clinical trial is available and appropriate for you. Below are current clinical trials the Pancreatic Cancer SPORE investigators are researching.

NeoAdjuvant

Neoantigen Vaccines in Pancreatic Cancer in the Window Prior to Surgery

The purpose of this research study is to assess the safety of a new vaccination called synthetic long peptide (SLP) vaccine. The vaccinations will be given in conjunction with an immunotherapy and will contain neoantigens that have been prioritized. Individuals will be randomly assigned to one of two groups: Group 1 will get the neoantigen vaccination after neoadjuvant chemotherapy and surgery, while Group 2 will receive the vaccine after neoadjuvant chemotherapy before surgery.

Novel CCR2 PET for Pancreatic Cancer Imaging and Prediction of Response to Standard and CCR2-Targeted Therapy

The purpose of this research study is to prolong the life and quality of life in participants with pancreatic ductal adenocarcinoma (PDAC) by identifying the patients that both respond and don’t respond to this therapy.

Testing the Immunologic Effects of CDX-301 and CDX-1140 in Resectable Pancreatic Cancer Patients

The purpose of this research study is to see if the addition of CDX-301 to CDX-1140 radically improves anti-tumor immunity in patients with pancreatic ductal adenocarcinoma (PDAC).

Metastatic

Study of Covalent Menin Inhibitor BMF-219 in Adult Patients With KRAS Driven Non-Small Cell Lung Cancer, Pancreatic Cancer, and Colorectal Cancer

The purpose of this research study is to determine the pharmacokinetics, pharmacodynamics, safety, and clinical activity of increasing dosages of a novel covalent minin inhibitor, BMF-219, taken orally in cycles of 28 days, either once daily or twice daily.

A Phase I Clinical Trial of CA-4948 in Combination With Gemcitabine and Nab-Paclitaxel in Metastatic or Unresectable Pancreatic Ductal Carcinoma

The purpose of this research study is to test the safety, side effects, and best dose of a novel oral inhibitor, emavusertib (CA-4948), in combination with traditional chemotherapy (gemcitabine and nab-paclitaxel) in treating patients with pancreatic ductal adenocarcinoma (PDAC) that has spread from where it first started (primary site) to other places in the body (metastatic) or cannot be removed by surgery (unresectable).

A Prospective Trial of Stereotactic Adaptive Radiation Therapy for Borderline Resectable/Locally Advanced Pancreatic Cancer: An Individualized Approach to Minimizing Gastrointestinal Toxicity (ARTIA-Pancreas)

The purpose of this research study is to show that ablatively dosed (50 Gy, 5fx) stereotactic adaptive radiation therapy will result in reduced toxicity when used to treat pancreatic adenocarcinomas that are medically inoperable, locally advanced, or borderline resectable. GI toxicity, overall survival, local control, quality of life, and workflow metrics will all be assessed in this study.

A Phase 1b/2a Study of Gemcitabine and Nab-paclitaxel in Combination With Avutometinib (VS-6766) and Defactinib in Patients With Previously Untreated Metastatic Adenocarcinoma of the Pancreas

The purpose of this research study is to assess the safety and efficacy of avutometinib (VS-6766) and defactinib in combination with standard chemotherapy (gemcitabine and nab-paclitaxel) in patients with pancreatic ductal adenocarcinoma (PDAC) who have been previously untreated.

Precision Promise Platform Trial for Metastatic Pancreatic Cancer

The purpose of this research study is to evaluate and compare multiple regimens for superiority in overall survival in first and/or second line metastatic ductal adenocarcinoma patients and determine which, if any, participants benefit from them.

Phase II Study of Stereotactic Body Radiotherapy and Focal Adhesion Kinase Inhibitor in Advanced Pancreas Adenocarcinoma

The purpose of this research study is to see if patients with locally advanced pancreas cancer have increased progression free survival (PFS) when they are treated with stereotactic body radiotherapy (SBRT) and an experimental drug regimen versus just receiving SBRT alone.

A Phase 1/1b/2 Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of AMG 193 Alone and in Combination With Docetaxel in Subjects With Advanced MTAP-null Solid Tumors

The purpose of Parts 1 and 2 of this research study is to evaluate the safety, tolerability, and to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of a new investigational targeted therapy, AMG 193, alone and in combination with a chemotherapy (docetaxel) in adult participants with metastatic or locally advanced solid tumors. The primary purpose of Part 3 of this research study is to evaluate the objective response rate (ORR) of AMG 193 in adult participants with metastatic or locally advanced solid tumors.

A Phase 1b/2 Study of HCW9218, a Bifunctional TGF-? Antagonist/IL-15 Protein Complex, for Advanced Pancreatic Cancer

 The purpose of this research study is to see how an immunotherapeutic agent, HCW9218, helps in patients with advanced/metastatic pancreatic cancer.

A Multicentric Phase 1/2 Trial to Evaluate the Safety and Efficacy of SOT102 as Monotherapy and in Combination With Standard of Care Treatment in Patients With Gastric and Pancreatic Adenocarcinoma

This trial will assess the MTD and RP2D of SOT102 administered as monotherapy (Part A) and in combination with first-line SoC treatment (mFOLFOX6 with nivolumab and nab-paclitaxel/ gemcitabine; Part B) and efficacy of SOT102 administered as monotherapy (Part C) and in combination with first-line SoC treatment (Part D) in patients with advanced inoperable or metastatic gastric/GEJ adenocarcinoma or inoperable or metastatic pancreatic adenocarcinoma.

SPORE in the News

• Pancreatic cancer research, clinical trials supported with $10.9 million NCI grant
• Immune-boosting compound makes immunotherapy effective against pancreatic cancer

• $9 million supports deep dive into breast, pancreatic cancers
• $10 million gift creates Bursky Center for Human Immunology and Immunotherapy 

Recent SPORE Publications

• Spatially restricted drivers and transitional cell populations cooperate with the microenvironment in untreated and chemo-resistant pancreatic cancer. Nature Genetics.
• Combination of ERK and autophagy inhibition as a treatment approach for pancreatic cancer. Nature Medicine.
• Dendritic cell paucity leads to dysfunctional immune surveillance in pancreatic cancer. Cancer Cell.
• Development of resistance to FAK inhibition in pancreatic cancer is linked to stromal depletion. Gut.Agonism of CD11b reprograms innate immunity to sensitize pancreatic cancer to immunotherapies. Science Translational Medicine.

Investigators and Staff

	Samuel Ballentine, MD Biospecimen Co-Investigator [email protected]
	Gregory Beatty, MD Project 3 Co-Leader Associate Professor of Medicine (Hematology-Oncology), University of Pennsylvania Perelman School of Medicine
	David DeNardo, PhD Project 1 Co-Leader, Project 3 Co-Investigator, Administrative Core Director, DRP Associate Director Associate Professor of Medicine, Pathology & Immunology. [email protected]
	Bettina Drake, PhD, MPH Administrative Core Co-Investigator Professor of Surgery [email protected]
	Ryan Fields, MD Biospecimen Core Directors & DRP Director Professor of Surgery [email protected]
	Feng Gao, MD, PhD, MPH Biostatistics Core Biostatistician Associate Professor of Surgery [email protected]
	William Gillanders, MD Project 2 Co-Leader & CEP Director Mary Culver Professor of Surgery [email protected]
	Peter Goedegebuure, PhD Project 2 Co-Investigator & Biospecimen Core Co-Investigator Associate Professor of Surgery [email protected]
	Patrick Grierson, MD, PhD Project 3 Co-Investigator [email protected]
	Malachi Griffith, PhD Biostatistics Core Co-Director [email protected]
	Christina Kasting, MBA, MSW SPORE Administrative Core Project Manager
	Kian-Huat Lim, MD, PhD Project 3 Co-Leader Assistant Professor of Medical Oncology [email protected]
	Esther Lu, PhD Biostatistics Core Biostatistician Associate Professor of Surgery [email protected]
	Pooja Navale, MBBS, MD Biospecimen Co-Investigator [email protected]
	Mark O’Hara, MD Project 3 Co-Investigator
	Katrina Pederson, MD Project 1 Co-Leader [email protected]
	Robert Schreiber, PhD Project 2 Co-Investigator AM & JM Bursky Distinguished Professor of Pathology & Immunology [email protected]
	Zach Skidmore Biostatistics Bioinformatician [email protected]
	Mark Watson, MD Biospecimen Core Associate Director Associate Professor of Pathology & Immunology [email protected]