Related Experiment Video
Updated: Aug 25, 2025
Molecular and Immunologic Techniques in a Genetically Engineered Mouse Model of Gastrointestinal Stromal Tumor
Published on: May 2, 2022
Current Immune Checkpoint Inhibitor Genetic Biomarker Exploration in Gastrointestinal Tumors
Jane E Rogers1, Kohei Yamashita2, Matheus Sewastjanow Silva2
1U.T. M.D. Anderson Cancer Center Pharmacy Clinical Programs, Houston, TX 77030, USA.
Abstract:
Immune checkpoint inhibitors have revolutionized cancer management. Some patients with gastrointestinal (GI) tract malignancy have experienced remarkable results. Here, in our review, we discuss predictive/prognostic GI tumor biomarkers that appear to correlate with benefits with this strategy. Remarkable progress has been made in certain subsets of patients including the potential for solid tumor patients to avoid local therapies such as radiation and/or surgery (organ preservation), which come with acute and chronic risks that have historically been the only curable strategies for these GI tumors. These results provide new and exciting strategies for solid tumor management. Unfortunately, immune checkpoint inhibitors can correlate with biomarkers, but benefits occur in a small subset of patients with GI malignancies. Most frequently, immune checkpoint inhibitors fail to induce response in GI malignancies due to the "cold" tumor microenvironment that protects cancer. Translational strategies are needed to develop effective combination strategies and novel biomarkers to overcome the intrinsic resistance.
Insights
Immune checkpoint inhibitors show promise for gastrointestinal (GI) cancers, but benefits are limited. Identifying predictive biomarkers is crucial for improving patient selection and overcoming resistance in "cold" tumors.
Area of Science:
- Oncology
- Immunology
Background:
- Immune checkpoint inhibitors (ICIs) have transformed cancer therapy, with notable successes in some gastrointestinal (GI) malignancies.
- ICIs offer potential organ preservation, reducing risks associated with traditional therapies like radiation and surgery for GI tumors.
Purpose of the Study:
- To review predictive and prognostic biomarkers for GI tumors that correlate with ICI treatment benefits.
- To discuss strategies for overcoming resistance to ICIs in GI malignancies.
Main Methods:
- Literature review of studies on immune checkpoint inhibitors and biomarkers in GI cancers.
- Analysis of current challenges, including the "cold" tumor microenvironment, hindering ICI efficacy.
Main Results:
- Certain biomarkers correlate with positive responses to ICIs in specific GI cancer subsets.
- However, ICIs benefit only a small fraction of GI malignancy patients due to intrinsic resistance.
Conclusions:
- Effective combination strategies and novel biomarkers are essential to enhance ICI efficacy in GI cancers.
- Addressing the "cold" tumor microenvironment is key to overcoming resistance and expanding ICI benefits.
