Latest immunotherapy of gastric cancer

Gastric cancer (GC) is a significant global health concern, affecting approximately ۹۹۰,۰۰۰ individuals annually and resulting in around ۷۳۸,۰۰۰ fatalities. To date, GC as the fourth most prevalent cancer and the second leading cause of cancer-related deaths. Several key risk factors contribute to the development of GC, including genetic predisposition, dietary habits, alcohol intake, tobacco use, and infections caused by Helicobacter pylori (H. pylori) and Epstein-Barr virus (EBV). H. pylori is identified as a primary carcinogen associated with GC, whereas EBV is linked to roughly ۱۰% of cases, although a clear causal relationship has not been established. Surgical intervention is a vital component of GC treatment, with optimal timing occurring when the tumor exhibits heightened sensitivity to chemotherapy. Recent advancements in treatment approaches, particularly the introduction of endoscopic resection and minimally invasive techniques, have markedly transformed therapeutic strategies over the past few decades. Adjuvant chemotherapy has demonstrated a statistically significant improvement in both overall survival and disease-free survival rates. The use of oral fluoropyrimidines may also prove beneficial in cases of advanced GC. In recent years, immunotherapy has emerged as a significant addition to GC treatment, often referred to as the "fifth pillar" of cancer therapy, with its application rapidly increasing. There are four main strategies employed in tumor immunotherapy: immune checkpoint inhibitors (ICIs), tumor vaccines, adoptive immunotherapy, and nonspecific immunomodulators. Current investigations into the use of immune checkpoint inhibitors for GC primarily focus on PD-۱ inhibitors such as nivolumab and pembrolizumab, the PD-L۱ inhibitor avelumab, and CTLA-۴ inhibitors including tremelimumab and ipilimumab. However, it is important to note that these therapies can be associated with immune-related adverse events, which, although often subtle, may be potentially life-threatening. Therapeutic cancer vaccines are a form of active immunotherapy designed to elicit a targeted immune response against tumor-specific antigens. These vaccines encompass various types, including autologous tumor cell vaccines, dendritic cell (DC) vaccines, peptide vaccines, and genetically modified vaccines. In ۲۰۱۰, Provenge became the first tumor vaccine to receive approval for the treatment of metastatic castration-resistant prostate cancer (CRPC). A phase I clinical trial involving vaccination with a peptide derived from LY۶K included six patients with advanced gastric cancer; results indicated that one patient experienced approximately a ۲۰% reduction in the size of liver metastases, while three others maintained stable disease. Given that the neoantigen strategy has not been extensively explored in clinical settings for gastric cancer, further research is essential to identify and evaluate the efficacy of these neoantigens.

کلیدواژه ها:

gastric cancer ، immunotherapy ، cancer vaccine ، immune checkpoint inhibitors