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Engineered Colon Cancer Tissue to Examine the Role of the Obese Microenvironment in Tumor Aggressiveness

Award Number: R01CA267170
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2022
PERIOD OF PERFORMANCE END DATE: 06/30/2027

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Engineered Colon Cancer Tissue to Examine the Role of the Obese Microenvironment in Tumor Aggressiveness - Abstract Modulation of the tumor microenvironment is known to promote the growth and survival of colorectal cancer (CRC) cells. Strong epidemiological evidence links certain types of human cancer, including CRC, with obesity, and the obese pathophysiological state has been shown experimentally to stimulate CRC tumor growth. However, the mechanisms involved are not fully known: in particular, the impact of the obese tumor microenvironment on CRC tumor cellular composition, stiffness, and ECM composition is not known. Further, pathophysiologically relevant, patient-specific models for investigating obesity-linked inflammation mediated changes in the obese, tumor microenvironment do not exist for CRC. Thus, the objective of the proposed project is to examine modulation of the tumor microenvironment and obesity-related CRC disease progression using tissue-engineered patient derived xenograft (PDX) CRC models validated through comparison to patient tumors and PDX tumors. Our collaborative team will achieve this objective by leveraging their unique combined interdisciplinary expertise in CRC, tissue engineering, obesity and metabolic disease, transcriptomics, proteomics, and bioinformatics. We will use our improved models of CRC that replicate the cues found in the obese, insulin resistant/pro- inflammatory tumor microenvironment to test the hypothesis that obesity alters stromal signaling in the consensus molecular subtype 4 (CMS4) tumor microenvironment. To test our hypothesis, we have developed a tissue-engineered platform that enables long-term in vitro culture of the patient-derived CRC cells and recapitulation of the native tumor microenvironment, particularly the stromal component. The following Specific Aims will be pursued: Aim 1. Determine the extent to which 3D in vitro engineered CMS4-derived CRC tissues recapitulate patient and PDX tumors; Aim 2. Determine and compare the obesity mediated changes in the stromal component and metastatic properties of CMS4-derived 3D engineered tissues and PDX tumors; and Aim 3. Examine 3D engineered tissues, PDX tumors, and patient tumors from obese CRC patients for engineered tissue refinement and obesity model validation. This investigator-initiated research effort is in response to FOA PAR-19-113, Cancer Tissue Engineering Collaborative: Enabling Biomimetic Tissue-Engineered Technologies for Cancer Research. Overall, these efforts, which employ state-of-the-art technologies to characterize and compare our paired models and human patient tumors in an in-depth and rigorous manner, will develop a portable tissue-engineering platform with robust cross-validation so that this tool can be used to uncover CRC subtype specific mechanisms of obesity-driven tumor progression, as well as other parameters affecting CRC morbidity and mortality.


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: 2025 ( Subtotal = $495,976 )
2025	2025	AUBURN UNIVERSITY	321-A INGRAM HALL	AUBURN	AL	36849	LEE	USA	Cancer Biology Research	000	4	6/16/2025	NON-COMPETING CONTINUATION	$495,976
														Subtotal = $495,976

Issue Date FY: 2024 ( Subtotal = $475,177 )
2024	2024	AUBURN UNIVERSITY	321-A INGRAM HALL	AUBURN	AL	36849	LEE	USA	Cancer Biology Research	000	3	7/3/2024	NON-COMPETING CONTINUATION	$475,177
														Subtotal = $475,177

Issue Date FY: 2023 ( Subtotal = $521,888 )
2023	2023	AUBURN UNIVERSITY	321-A INGRAM HALL	AUBURN	AL	36849	LEE	USA	Cancer Biology Research	000	2	6/30/2023	NON-COMPETING CONTINUATION	$495,888
2023	2023	AUBURN UNIVERSITY	321-A INGRAM HALL	AUBURN	AL	36849	LEE	USA	Cancer Biology Research	001	2	9/14/2023	NON-COMPETING CONTINUATION	$26,000
														Subtotal = $521,888

Issue Date FY: 2022 ( Subtotal = $500,160 )
2022	2022	AUBURN UNIVERSITY	107 SAMFORD HALL	AUBURN	AL	36849	LEE	USA	Cancer Biology Research	000	1	6/20/2022	NEW	$500,160
														Subtotal = $500,160

Grand Total All Awards = $1,993,201

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Engineered Colon Cancer Tissue to Examine the Role of the Obese Microenvironment in Tumor Aggressiveness

Award Number: R01CA267170

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/01/2022

PERIOD OF PERFORMANCE END DATE: 06/30/2027

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