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Biomarkers for Predicting Response to Personalized Immunotherapy in Gastric Cancer
Moonsik Kim1,2, Ji Yun Jeong1,2, An Na Seo1,2
1Department of Pathology, School of Medicine, Kyungpook National University, 136-gil 90, Chilgokjungang-daero, Buk-gu, Daegu 41405, Republic of Korea.
Abstract:
Despite advances in diagnostic imaging, surgical techniques, and systemic therapy, gastric cancer (GC) is the third leading cause of cancer-related death worldwide. Unfortunately, molecular heterogeneity and, consequently, acquired resistance in GC are the major causes of failure in the development of biomarker-guided targeted therapies. However, by showing promising survival benefits in some studies, the recent emergence of immunotherapy in GC has had a significant impact on treatment-selectable procedures. Immune checkpoint inhibitors (ICIs), widely indicated in the treatment of several malignancies, target inhibitory receptors on T lymphocytes, including the programmed cell death protein (PD-1)/programmed death-ligand 1 (PD-L1) axis and cytotoxic T-lymphocyte-associated protein 4 (CTLA4), and release effector T-cells from negative feedback signals. In this article, we review currently available predictive biomarkers (including PD-L1, microsatellite instability, Epstein-Barr virus, and tumor mutational burden) that affect the ICI treatment response, focusing on PD-L1 expression. We further briefly describe other potential biomarkers or mechanisms for predicting the response to ICIs in GC. This review may facilitate the expansion of the understanding of biomarkers for predicting the response to ICIs and help select the appropriate therapeutic approaches for patients with GC.
Insights
Gastric cancer (GC) immunotherapy shows promise, but resistance is a challenge. This review explores biomarkers like PD-L1 to predict immune checkpoint inhibitor (ICI) response in GC patients.
Area of Science:
- Oncology
- Immunology
- Gastroenterology
Background:
- Gastric cancer (GC) remains a leading cause of cancer death globally.
- Molecular heterogeneity and acquired resistance impede targeted therapies for GC.
- Immunotherapy, particularly immune checkpoint inhibitors (ICIs), offers new hope for GC treatment.
Purpose of the Study:
- To review predictive biomarkers for ICI response in gastric cancer.
- To focus on programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) axis and other biomarkers.
- To aid in selecting optimal therapeutic strategies for GC patients.
Main Methods:
- Literature review of current predictive biomarkers for ICI therapy in GC.
- Analysis of biomarkers including PD-L1, microsatellite instability, Epstein-Barr virus, and tumor mutational burden.
- Discussion of potential novel biomarkers and response mechanisms.
Main Results:
- Several biomarkers, including PD-L1 expression, microsatellite instability, Epstein-Barr virus, and tumor mutational burden, influence ICI treatment response in GC.
- PD-L1 expression is a key focus for predicting ICI efficacy.
- Emerging biomarkers and mechanisms are also being investigated.
Conclusions:
- Accurate biomarker identification is crucial for effective ICI therapy in GC.
- Understanding these biomarkers can guide treatment selection and improve patient outcomes.
- Further research into novel biomarkers will enhance personalized medicine approaches for GC.
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