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The impact of exposure to allergic inflammation on esophageal carcinogenesis

Award Number: R21CA256465
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/01/2020
PERIOD OF PERFORMANCE END DATE: 11/30/2022

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The impact of exposure to allergic inflammation on esophageal carcinogenesis - Project Summary Esophageal cancer is the eighth most common cancer and sixth leading cause of cancer mortality worldwide. Chronic reflux-associated esophagitis, termed gastroesophageal reflux disease (GERD), is a primary risk factor for development of esophageal adenocarcinoma. Eosinophilic esophagitis (EoE) represents food allergen-mediated esophagitis characterized by esophageal eosinophilia. In contrast to patients with reflux esophagitis, epidemiological data indicates that EoE patients fail to develop esophageal cancer despite the presence of chronic esophageal inflammation. A negative correlation between allergic inflammation and cancer risk has been identified in a variety of organs via population-based studies; however, functional investigations are necessary to define the relationship between allergy and cancer as well as to determine the feasibility of approaches for leveraging allergic inflammation to improve clinical outcomes in cancer patients. To examine the relationship between EoE and cancer, we paired murine models of the two conditions. Our robust preliminary data indicate that exposure to EoE inflammation limits esophageal carcinogenesis in vivo. We hypothesize that EoE inflammation limits esophageal carcinogenesis by activating anti-tumor responses in the immune and epithelial cell compartments. We will test this hypothesis by pursuing the following Specific Aims: Aim 1: Identify the immune-mediated mechanisms responsible for tumor cell apoptosis induced by EoE inflammation. Aim 2: Delineate the impact of EoE inflammation upon esophageal epithelial cells in the context of carcinogenesis. These studies provide the first functional investigation of the relationship between EoE and esophageal cancer with the potential to unveil novel mechanisms for targeting the allergic immune response and/or allergy-mediated esophageal epithelial fate decisions to improve clinical care for cancer patients. These developmental R21 studies will identify the direct cellular/molecular mechanisms through which the EoE influences the epithelial and immune cell compartments to limit esophageal carcinogenesis. A future R01 proposal will aggressively pursue identified mechanisms in preclinical and clinical models to meet our long- term goal of defining novel strategies for improving esophageal cancer prevention, diagnosis, monitoring, and therapy. As a negative association between allergic inflammation and cancer has been identified in various organs, findings from this study may have broad implications for cancer prevention and therapy.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2022	TEMPLE UNIVERSITY-OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	1805 N BROAD ST	PHILADELPHIA	PA	19122	PHILADELPHIA	USA	Cancer Treatment Research	000	2	11/7/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $181,543 )
2022	2022	TEMPLE UNIVERSITY-OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	1801 N BROAD ST	PHILADELPHIA	PA	19122	PHILADELPHIA	USA	Cancer Treatment Research	000	2	11/17/2021	NON-COMPETING CONTINUATION	$166,721
2022	2022	TEMPLE UNIVERSITY-OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	1801 N BROAD ST	PHILADELPHIA	PA	19122	PHILADELPHIA	USA	Cancer Treatment Research	001	2	5/26/2022	NON-COMPETING CONTINUATION	$14,822
														Subtotal = $181,543

Issue Date FY: 2021 ( Subtotal = $222,296 )
2021	2021	TEMPLE UNIVERSITY-OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	1801 N BROAD ST	PHILADELPHIA	PA	19122	PHILADELPHIA	USA	Cancer Treatment Research	000	1	11/25/2020	NEW	$222,296
														Subtotal = $222,296

Grand Total All Awards = $403,839

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The impact of exposure to allergic inflammation on esophageal carcinogenesis

Award Number: R21CA256465

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 12/01/2020

PERIOD OF PERFORMANCE END DATE: 11/30/2022

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