# Role of Erbb3 kinase activity in colorectal tumorigenesis.

> **NIH NIH R01** · CASE WESTERN RESERVE UNIVERSITY · 2024 · $136,315

## Abstract

ABSTRACT
Immunotherapy is the standard of care and an effective treatment for colorectal cancers with deficient
mismatch repair proteins (dMMR). The deficiency contributes to high tumor mutational burden in the tumors
and the generation of neoantigens that can activate the immune system. However, despite the effectiveness of
immunotherapy for dMMR colorectal cancers, up to half of patients with dMMR cancers do not derive clinical
benefit from the treatment. Intrinsic or acquired resistance to immunotherapy may limit clinical efficacy and
thus a better understanding of the factors and mechanisms that lead to resistance is needed. The growing
interest in using immunotherapy in the neoadjuvant setting for dMMR tumors further underscores the need to
prevent or limit resistance to immunotherapy. Tumor intrinsic factors and mechanisms related to molecular
alterations and changes in signaling pathways likely contribute to pre-existing and acquired immunotherapy
resistance. Targeting tumor-intrinsic mechanisms in combination with immunotherapy may improve overall
survival of patients with dMMR colorectal cancers. Our main goal for this study is to identify and validate genes
and signaling pathways associated with resistance to immunotherapy in dMMR colorectal cancer using a
mouse model and gene-editing tools. We will validate a select set of genes most likely to play a role in
resistance to immunotherapy. In the long term, data from this project will guide our efforts to determine the
mechanisms of immunotherapy resistance and to design highly effective combination therapies that either
anticipate or limit the development of resistance to immunotherapy.

## Key facts

- **NIH application ID:** 11063440
- **Project number:** 3R01CA256791-04S1
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** Zhenghe Wang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $136,315
- **Award type:** 3
- **Project period:** 2021-02-09 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11063440

## Citation

> US National Institutes of Health, RePORTER application 11063440, Role of Erbb3 kinase activity in colorectal tumorigenesis. (3R01CA256791-04S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11063440. Licensed CC0.

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