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

> **NIH NIH R37** · SLOAN-KETTERING INST CAN RESEARCH · 2024 · $45,002

## 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. We believe that both the paucity of models and the lack of predictive tools
can be addressed by patient-derived tumoroids. Tumoroids can be grown in 3-dimensional culture ex vivo or
implanted into mice, so they offer 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. The tumoroids will be analyzed in ex vivo culture and in two mouse models: the endoluminal
implantation model and a conventional flank injection model. 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. Of particular interest is whether individual human rectal cancers are more
accurately modeled by endoluminal implantation than by flank injection. 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. The online platform will be built
within our institution's cancer genomics portal, then integrated into the NCIP Hub. We have assembled a
collaborative team with expertise in colorectal surgical oncology, radiation oncology, and pathology; organoids;
mouse models; biostatistics; and bioinformatics. 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 sti...

## Key facts

- **NIH application ID:** 10977484
- **Project number:** 3R37CA248289-05S1
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** Jesse Joshua Smith
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $45,002
- **Award type:** 3
- **Project period:** 2020-03-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10977484

## Citation

> US National Institutes of Health, RePORTER application 10977484, Expansion of Tumoroid Models for Precise Treatment of the Rectal Cancer Patient (3R37CA248289-05S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10977484. Licensed CC0.

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