Revolutionizing Gastric Cancer Care: Recent Advances and Future Prospects
Revolutionizing Gastric Cancer Care: Recent Advances and Future Prospects
Amir Abbas Alviri,1,*Mahdi Bagheri,2
1. Department of Biology, Islamic Azad University, Science and Research Branch 2. Gastroenterohepatology Research Center, Shiraz University of Medical Sciences
Introduction: Gastric cancer (GC) is one of the most common cancers globally, with most patients diagnosed at advanced stages due to the subtlety of early symptoms and the infrequency of regular screening. Over the past few years, there have been significant advancements in the systemic treatment of GC, including chemotherapy, targeted therapies, and immunotherapy. For resectable GC, perioperative chemotherapy has become the standard approach. Current research is exploring the potential benefits of integrating targeted therapies and immunotherapies in both perioperative and adjuvant settings. These include treatments such as mono-immunotherapy, dual checkpoint inhibitors, anti-angiogenic drugs, and biomarker-targeted therapies.
Methods: Radical surgery remains the primary treatment for resectable gastric cancer. To minimize the risk of recurrence and improve long-term survival, therapies such as perioperative chemotherapy, adjuvant chemotherapy, and adjuvant chemoradiotherapy have been developed. Clinical trials have shown that perioperative chemotherapy, in particular, significantly improves outcomes in comparison to surgery alone.
Adjuvant chemotherapy is also recommended for patients with stage II or stage III cancer who have undergone surgery. Recent trials, particularly in Asian populations, have demonstrated significantly higher survival rates with this approach.
For advanced gastric cancer, anti-HER2 and anti-vascular endothelial growth factor (VEGF) agents have become standard treatments. However, there is ongoing research to better understand the role of targeted therapies in the perioperative or adjuvant settings.
Programmed death 1 (PD-1) inhibitors have gained approval for first- and third-line treatment of metastatic gastric cancer in various countries, backed by several phase III clinical trials. Despite these advancements, the role of immune checkpoint inhibitors in resectable gastric cancer remains under investigation, with multiple trials currently underway.
Cytotoxic agents, including fluoropyrimidines, platinum derivatives, taxanes, and irinotecan, form the backbone of therapy for advanced gastric carcinoma. Fluoropyrimidines (such as fluorouracil, capecitabine, and S-1) combined with platinum-based drugs are often used as first-line treatments, with oxaliplatin being as effective as cisplatin. The phase III SOX-GC study demonstrated improved survival outcomes with the SOX regimen compared to the SP regimen for patients with diffuse or mixed-type gastric cancer.
Immune checkpoint inhibitors (ICIs), either as monotherapy or in combination with other treatments, have shown promising anti-tumor activity in gastrointestinal cancers. For instance, the phase III ToGA study established trastuzumab combined with chemotherapy as the standard first-line treatment for HER2-positive advanced gastric cancer. Additionally, margetuximab, an Fc-engineered anti-HER2 monoclonal antibody, has been developed to target the same epitope as trastuzumab but with enhanced binding to specific single-nucleotide polymorphisms of the activating Fc receptor (CD16A).
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Results: While significant advancements have been made in the treatment of gastric cancer, including the development of chemotherapy, targeted therapies, and immunotherapies, challenges remain, particularly in early diagnosis and recurrence prevention. Perioperative chemotherapy has become the standard for resectable GC, and ongoing research continues to explore the integration of targeted therapies and immune checkpoint inhibitors. Additionally, treatments like anti-HER2 and anti-VEGF agents offer new options for advanced cases. However, further investigation is needed to optimize therapeutic strategies, and expanding endoscopic screening programs is crucial for improving early detection and long-term survival outcomes in gastric cancer patients.
Conclusion: Despite these transformative advances in GC treatment, further research is needed to address remaining challenges, such as early diagnosis, reducing recurrence rates, and optimizing therapy options. Implementing widespread endoscopic screening programs is essential to improving early detection and increasing survival rates in gastric cancer patients.