Tuesday, July 1, 2025 7/1/2025

Expansion of Tumoroid Models for Precise Treatment of the Rectal Cancer Patient

Award Number: R37CA248289
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/01/2025
PERIOD OF PERFORMANCE END DATE: 02/28/2027

Group Awards By:

View Award Description

Expansion of Tumoroid Models for Precise Treatment of the Rectal Cancer Patient - PROJECT SUMMARY/ABSTRACT: We propose to develop rectal cancer organoids (tumoroids) as individualized models and to build a large rectal cancer tumoroid repository. Research on rectal cancers is hampered by the paucity of models. Of the few existing in vivo models of rectal cancer, none place the tumors in the rectal lumen, so the models fail to mimic the correct anatomic environment and local invasion. The existing models also have not been observed to metastasize. Another problem is that we lack accurate means to predict whether individual rectal cancer patients will respond to chemotherapy or radiation, both of which are part of the current standard of care. These challenges can be addressed by patient-derived tumoroids, which can be grown in 3-dimensional culture ex vivo or implanted into mice, offering a flexible research platform. In preliminary results, we have derived tumoroid lines from multiple patients' rectal cancers and found them to resemble the corresponding patient tumors. The tumoroids, when implanted in mice endoluminally (i.e. in the rectum), formed locally invasive tumors capable of metastasis. Moreover, we found tumoroids to have clinically relevant responses to chemotherapy and radiation. Thus, drawing from these preliminary data, we hypothesize that rectal cancer tumoroids mirror the traits of their original tumors, can be used to predict patients' response to therapy, and, when implanted endoluminally into mice, can serve as an optimal model of rectal cancer. We plan to develop 100 new tumoroids, which we expect to encompass much of the diversity of human rectal adenocarcinoma. Tumoroids will be analyzed in ex vivo culture and in the endoluminal implantation and conventional flank injection models. In these settings, we will test whether the tumoroid accurately reflects its tumor of origin in terms of mutations, histology, and gene expression. We will determine whether response of the tumoroids to patient-specific chemotherapy and radiation can predict the corresponding patient's response, and whether individual human rectal cancers are more accurately modeled by endoluminal implantation than by flank injection. Leveraging our tumoroid biorepository, we will also identify molecular drivers of chemotherapy response by comparing tumoroids derived from patients with complete response to those with incomplete response and determine the mechanism of chemoresistance in SMAD4-deficient tumoroids. Finally, to integrate our findings into a comprehensive platform for broad use, we will develop a rectal cancer tumoroid biorepository seamlessly integrated with online pathologic, genomic, and model-specific information. We anticipate that the proposed research will credential tumoroids as accurate models for rectal cancer research and for predicting patient responses to therapy. The large tumoroid biorepository is likely to stimulate research on new treatments for rectal cancer. The ultimate result will be new treatment options and better treatment selection for patients affected by this deadly disease.


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 = $545,622 )
2025	2025	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Cancer Biology Research	000	6	3/3/2025	EXTENSION WITH OR WITHOUT FUNDS	$545,622
														Subtotal = $545,622

Issue Date FY: 2024 ( Subtotal = $625,686 )
2024	2024	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVENUE	NEW YORK	NY	10065	NEW YORK	USA	Cancer Biology Research	002	5	4/17/2024	NON-COMPETING CONTINUATION	$30,563
2024	2024	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVENUE	NEW YORK	NY	10065	NEW YORK	USA	Cancer Biology Research	003	5	4/17/2024	SUPPLEMENT FOR EXPANSION	$2,368
2024	2024	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVENUE	NEW YORK	NY	10065	NEW YORK	USA	Cancer Biology Research	000	5	2/13/2024	NON-COMPETING CONTINUATION	$550,121
2024	2024	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVENUE	NEW YORK	NY	10065	NEW YORK	USA	Cancer Biology Research	001	5	2/14/2024	SUPPLEMENT FOR EXPANSION	$42,634
														Subtotal = $625,686

Issue Date FY: 2023 ( Subtotal = $704,385 )
2023	2023	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Cancer Biology Research	001	4	5/23/2023	SUPPLEMENT FOR EXPANSION	$105,363
2023	2023	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Cancer Biology Research	000	4	2/15/2023	NON-COMPETING CONTINUATION	$599,022
														Subtotal = $704,385

Issue Date FY: 2022 ( Subtotal = $611,246 )
2022	2022	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Cancer Biology Research	000	3	2/17/2022	NON-COMPETING CONTINUATION	$550,119
2022	2022	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Cancer Biology Research	001	3	5/20/2022	NON-COMPETING CONTINUATION	$61,127
														Subtotal = $611,246

Issue Date FY: 2021 ( Subtotal = $611,246 )
2021	2021	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Cancer Biology Research	000	2	2/10/2021	NON-COMPETING CONTINUATION	$611,246
														Subtotal = $611,246

Issue Date FY: 2020 ( Subtotal = $611,246 )
2020	2020	SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH	1275 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Cancer Biology Research	000	1	2/25/2020	NEW	$611,246
														Subtotal = $611,246

Grand Total All Awards = $3,709,431

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Expansion of Tumoroid Models for Precise Treatment of the Rectal Cancer Patient

Award Number: R37CA248289

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 03/01/2025

PERIOD OF PERFORMANCE END DATE: 02/28/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer