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Current treatment and recent progress in gastric cancer.
Literature Information
| DOI | 10.3322/caac.21657 |
|---|---|
| PMID | 33592120 |
| Journal | CA: a cancer journal for clinicians |
| Impact Factor | 232.4 |
| JCR Quartile | Q1 |
| Publication Year | 2021 |
| Times Cited | 911 |
| Keywords | adenocarcinoma, gastric cancer, immunotherapy, molecular subtypes, stomach neoplasms |
| Literature Type | Journal Article, Research Support, Non-U.S. Gov't, Review |
| ISSN | 0007-9235 |
| Pages | 264-279 |
| Issue | 71(3) |
| Authors | Smita S Joshi, Brian D Badgwell |
TL;DR
Gastric cancer, a leading cause of cancer mortality worldwide, exhibits biological differences between Eastern and Western tumors that complicate treatment standardization; however, advancements in triplet chemotherapy and molecular subtype classification are paving the way for personalized therapies. The identification of key biomarkers such as MSI and PD-L1 is enhancing systemic therapy strategies, but further research is needed for less differentiated gastric adenocarcinoma subtypes lacking immunotherapy markers.
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adenocarcinoma · gastric cancer · immunotherapy · molecular subtypes · stomach neoplasms
Abstract
Gastric cancer is not a top-10 malignancy in the United States but represents one of the most common causes of cancer death worldwide. Biological differences between tumors from Eastern and Western countries add to the complexity of identifying standard-of-care therapy based on international trials. Systemic chemotherapy, radiotherapy, surgery, immunotherapy, and targeted therapy all have proven efficacy in gastric adenocarcinoma; therefore, multidisciplinary treatment is paramount to treatment selection. Triplet chemotherapy for resectable gastric cancer is now accepted and could represent a plateau of standard cytotoxic chemotherapy for localized disease. Classification of gastric cancer based on molecular subtypes is providing an opportunity for personalized therapy. Biomarkers, in particular microsatellite instability (MSI), programmed cell death ligand 1 (PD-L1), human epidermal growth factor receptor 2 (HER2), tumor mutation burden, and Epstein-Barr virus, are increasingly driving systemic therapy approaches and allowing for the identification of populations most likely to benefit from immunotherapy and targeted therapy. Significant research opportunities remain for the less differentiated histologic subtypes of gastric adenocarcinoma and those without markers of immunotherapy activity.
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Primary Questions Addressed
- How do the biological differences between Eastern and Western gastric cancer tumors influence treatment protocols?
- What are the implications of molecular subtype classification for the future of personalized therapy in gastric cancer?
- In what ways can biomarkers like MSI and PD-L1 improve the selection of patients for immunotherapy in gastric cancer?
- What are the challenges and opportunities in researching less differentiated histologic subtypes of gastric adenocarcinoma?
- How does the integration of triplet chemotherapy impact long-term outcomes for patients with resectable gastric cancer?
Key Findings
Research Background and Objectives
Gastric cancer, while not a leading malignancy in the United States, is a major cause of cancer mortality globally. The biological differences in tumors between Eastern and Western populations complicate the establishment of standardized treatment protocols based on international clinical trials. This study aims to explore the evolving landscape of gastric cancer treatment, emphasizing the role of personalized medicine and the integration of molecular biomarkers in therapeutic strategies.
Main Methods/Materials/Experimental Design
The research employs a comprehensive review of existing literature on gastric cancer treatment modalities, including systemic chemotherapy, radiotherapy, surgery, immunotherapy, and targeted therapies. The classification of gastric cancer by molecular subtypes is highlighted as a pivotal method for developing personalized treatment approaches. The following flowchart illustrates the key components of the study's methodology:
Key Results and Findings
- Triplet Chemotherapy: Accepted as a standard for resectable gastric cancer, indicating a plateau in cytotoxic chemotherapy effectiveness for localized disease.
- Molecular Subtypes: The classification of gastric cancer based on molecular characteristics is gaining traction, enabling personalized treatment strategies.
- Biomarkers: Key biomarkers such as MSI, PD-L1, HER2, tumor mutation burden, and Epstein-Barr virus are increasingly guiding treatment decisions, particularly for immunotherapy and targeted therapies.
| Biomarker | Role in Therapy |
|---|---|
| Microsatellite Instability (MSI) | Indicator for immunotherapy response |
| Programmed Cell Death Ligand 1 (PD-L1) | Target for immunotherapy |
| Human Epidermal Growth Factor Receptor 2 (HER2) | Target for targeted therapy |
| Tumor Mutation Burden | Prognostic and predictive marker |
| Epstein-Barr Virus | Potential target for immunotherapy |
Main Conclusions/Significance/Innovation
The study underscores the importance of a multidisciplinary approach in the treatment of gastric cancer, advocating for personalized therapy driven by molecular characterization. The identification of specific biomarkers not only enhances the efficacy of treatment strategies but also facilitates the selection of patients who are most likely to benefit from advanced therapeutic options, thereby improving clinical outcomes.
Research Limitations and Future Directions
- Histological Subtypes: There is a significant gap in research concerning less differentiated histological subtypes of gastric adenocarcinoma, which may respond differently to therapies.
- Immunotherapy Activity: Future studies should focus on populations without established markers of immunotherapy activity to explore alternative therapeutic avenues.
- Global Disparities: The differences in gastric cancer biology between Eastern and Western populations necessitate further investigation to tailor treatments that are effective across diverse genetic backgrounds.
Future research should aim to refine treatment protocols based on comprehensive biomarker profiling and expand the understanding of gastric cancer's molecular landscape to enhance patient outcomes globally.
References
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Literatures Citing This Work
- Everything, in Retrospect, is Obvious. - Brian Badgwell - Annals of surgical oncology (2021)
- The emerging role of miR-10 family in gastric cancer. - Fang Liu;Yanfen Shi;Zuolong Liu;Ziyi Li;Wei Xu - Cell cycle (Georgetown, Tex.) (2021)
- The RNA-Binding Protein NELFE Promotes Gastric Cancer Growth and Metastasis Through E2F2. - Changyu Chen;Qiang Zheng;Shubo Pan;Wenzheng Chen;Jianfeng Huang;Yi Cao;Yi Tu;Zhengrong Li;Changjun Yu;Zhigang Jie - Frontiers in oncology (2021)
- Prognostic Role of Receptor Tyrosine Kinase-Like Orphan Receptors in Intestinal-Type Gastric Cancer. - Rajeev Nema;Priti Patel;Ashok Kumar - Asian Pacific journal of cancer prevention : APJCP (2021)
- Comprehensive Analysis of the Value of SMYD Family Members in the Prognosis and Immune Infiltration of Malignant Digestive System Tumors. - Donghui Liu;Xuyao Wang;Enhong Shi;Liru Wang;Minghao Nie;Long Li;Qingxin Jiang;Pengyu Kong;Shuai Shi;Chao Wang;Sen Yan;Zhihui Qin;Shuang Zhao - Frontiers in genetics (2021)
- Effect of LAMA4 on Prognosis and Its Correlation with Immune Infiltration in Gastric Cancer. - Mingming Wang;Changzheng Li;Ying Liu;Zuomin Wang - BioMed research international (2021)
- Safety and Efficacy of Laparoscopic Versus Open Gastrectomy in Patients With Advanced Gastric Cancer Following Neoadjuvant Chemotherapy: A Meta-Analysis. - Xu-Liang Liao;Xian-Wen Liang;Hua-Yang Pang;Kun Yang;Xin-Zu Chen;Xiao-Long Chen;Kai Liu;Lin-Yong Zhao;Wei-Han Zhang;Jian-Kun Hu - Frontiers in oncology (2021)
- LncRNA PITPNA-AS1 promotes gastric cancer by increasing SOX4 expression via inhibition of miR-92a-3p. - Licheng Liu;Anna Dai;Zao Zhang;Meiying Ning;Dong Han;Li Li;Zhuangzhuang Li - Aging (2021)
- Efficiency of complete omentectomy in patients with resectable gastric cancer: a meta‑analysis and systematic review. - Akao Zhu;Guang Yin;Xinchun Liu;Wencheng Kong;Yu Zhang;Yuqiang Shan;Rongchao Ying;Jian Zhang;Chunhua Zhou - BMC gastroenterology (2021)
- Tumor-Infiltrating Neutrophils and Non-Classical Monocytes May Be Potential Therapeutic Targets for HER2negative Gastric Cancer. - Juhee Jeong;Duk Ki Kim;Ji-Hyeon Park;Do Joong Park;Hyuk-Joon Lee;Han-Kwang Yang;Seong-Ho Kong;Keehoon Jung - Immune network (2021)
... (901 more literatures)
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