<p>Current Molecular Targeted Agents for Advanced Gastric Cancer</p>

Abstract

Gastric cancer is the third leading cause of malignant tumor-related mortality worldwide. Traditional cytotoxic agents prolong the overall survival and progression-free survival of patients with advanced gastric cancer (AGC) compared to that with best supportive care. Due to the occurrence of serious adverse drug reactions that result in discontinued treatment, the survival benefit in AGC remains unsatisfactory. Systemic chemotherapy regimens have changed greatly, especially since the introduction of trastuzumab. Nevertheless, HER2 positivity is present in only approximately 20% of tumors. Due to the genetic heterogeneity and complexity of patients, there are many studies in progress that are exploring novel targeted drugs as an alternative to chemotherapy or adjuvant treatment in early-stage, progressive, and advanced gastric cancer. On the basis of the differences in gene expression profiles among patients, searching for specific and sensitive predictive biomarkers is important for identifying patients who will benefit from a specific targeted drug. With the development of targeted therapies and available chemotherapeutic drugs, there is no doubt that, over time, more patients will achieve better survival outcomes. Recently, immune checkpoint blockade has been well developed as a promising anticancer strategy. This review outlines the currently available information on clinically tested molecular targeted drugs and immune checkpoint inhibitors for AGC to provide support for decision-making in clinical practice.

Crosstalk Between Mesenchymal Stromal Cells and Tumor-Associated Macrophages in Gastric Cancer

“…Gastric cancer is the fourth most commonly diagnosed malignant tumor worldwide and considered as the third leading cause of cancer-related death, following lung and liver cancer ( 1 ). Despite a drop in the mortality rate due to the advancements of pathological diagnostic programs and therapeutic approaches, gastric cancer remains a prevalent disease with poor prognosis ( 2 , 3 ).…”

Perioperative Safety and Effectiveness of Neoadjuvant Therapy with Fluorouracil, Leucovorin, Oxaliplatin, and Docetaxel Plus Apatinib in Locally Advanced Gastric Cancer

“…15 Apatinib is in widespread use, and has been applied to various gastric cancer scenarios. 16 Apatinib combined with chemotherapy can achieve a promising efficacy and acceptable safety in adjuvant therapy for advanced gastric cancer or neoadjuvant therapy for LAGC. [17][18][19] As a major gastric cancer diagnosis and treatment center in central China, we has already treated many gastric cancer patients with FLOT or apatinib.…”

M1-like TAMs are required for the efficacy of PD-L1/PD-1 blockades in gastric cancer

“…For localized gastric cancer, curative resection is a standard and preferred treatment, but the recurrence rate remains high, with a five-year survival of less than 25% and median overall survival (OS) of 7 to 10 months after diagnosis. 2,3 For unresectable or metastatic advanced GC, cytotoxic chemotherapy is mostly used. However, cytotoxic chemotherapy is nonspecific and has serious adverse reactions, the outcomes being usually poor.…”

“…2,4 Although molecular targeted agents such as anti-HER2 monoclonal antibody and vascular endothelial growth factor receptor-2 (VEGFR-2) inhibitors have been introduced into clinical practice in recent years, the efficacy was limited. 2,5 Recently, immune checkpoint inhibitors targeting PD-1/ PD-L1 have become the most revolutionary treatment in solid tumors, and the PD-1/PD-L1 blockades have been recommended as first-line treatments for advanced non-small-cell lung cancer (NSCLC) and melanoma. And PD-1/PD-L1 blockades in combination with chemotherapy in patients with advanced gastric/gastroesophageal junction cancer have demonstrated encouraging efficacy.…”