Recent Developments of Systemic Chemotherapy for Gastric Cancer

Abstract

Gastric cancer (GC) is a molecularly heterogeneous disease. Its molecular background, epidemiology, and standard of care are quite different between Eastern and Western countries. Many efforts have been made in developing more effective surgeries and adjuvant chemotherapies for resectable GC in each region. Recently, an intensive combination of cytotoxic agents has been established as a new standard of adjuvant treatment. Meanwhile, palliative chemotherapy is a uniform standard treatment for unresectable GC worldwide. Recently, one of the most remarkable advances in therapy for unresectable GC has been the approval of immune checkpoint inhibitors (ICIs). The use of ICIs as frontline treatment is currently being investigated. In addition, novel combinations of ICIs and targeted drugs are being evaluated in clinical trials. Despite these advances, the complex biology of GC has resulted in the failure of targeted therapies, with the exceptions of HER2-targeted trastuzumab and VEGFR2-targeted ramucirumab. GC harbors many redundant oncogenic pathways, and small subsets of tumors are driven by different specific pathways. Therefore, a combination strategy simultaneously inhibiting several pathways and/or stricter patient selection for better response to targeted drugs are needed to improve clinical outcomes in this field.

PolG Inhibits Glycolysis by Suppressing PKM2 Phosphorylation Resulting Reduced Gastric Cancer Proliferation

“…GC samples with survival data and gene expression pro les were obtained from the GSE62254 dataset as shown in Table 1. The sample characteristics of GSE62254 were consistent with randomized clinical studies of GC [3,14,15]. The prognostic value of PolG was evaluated by Kaplan-Meier analysis which showed that low expression of PolG was associated with worse overall survival (OS, log-rank P < 0.001) as well as progression-free survival (PFS, log-rank P < 0.001) (Fig.…”

“…Major efforts have been made in GC treatment including targeted therapies such as HER2-targeted trastuzumab, VEGFR2-targeted ramucirumab, and immune checkpoint inhibitors (ICIs) [2]. In addition to these improvements, the complex biology of GC often results in treatment failure and therapeutic resistance [3]. Therefore, it is necessary to further explore novel treatment targets, and adopt comprehensive treatment approaches to deliver better patient outcomes in GC.…”

Circular RNAs in Gastric Cancer: Potential Biomarkers and Therapeutic Targets

“…Chemotherapy as an indispensable adjuvant treatment strategy has been routinely applied to the advanced stage GC. To effectively suppress tumor growth and metastasis, some combination regimens can simultaneously restrain several oncogenic pathways which are recommended to use [ 93 ]. However, how to alleviate the chemotherapy resistance and toxicity has become an urgent issue in order to provide better treatment of GC patients.…”

From Interconnection between Genes and Microenvironment to Novel Immunotherapeutic Approaches in Upper Gastro-Intestinal Cancers—A Multidisciplinary Perspective

“…Furthermore, two randomized phase II trials are currently ongoing: the DANTE trial (NCT 03421288) evaluating peri-operative use of atezolizumab (anti-PD-L1 antibody) combined with FLOT (docetaxel, oxaliplatin, leucovorin and 5-fluorouracil) [ 160 ] and the IMAGINE NCT04062656 randomized, four-arm, chemotherapy-controlled modular trial in subjects with histologically confirmed, resectable GC or GEJ adenocarcinoma. An increase to 35% is estimated to be clinically relevant when patients are treated with either nivolumab in combination with chemotherapy or nivolumab and another immuno-oncology agent (e.g., ipilimumab or relatlimab) [ 161 , 162 ]. Great interest is now addressed to the combination of ICIs and targeted molecules, which seems to be promising although findings are still afar to be conclusive.…”