Emerging Therapies in the Management of Advanced-Stage Gastric Cancer

Abstract

Globally, gastric malignancy contributes to significant cancer-related morbidity and mortality. Despite a recent approval of two targeted agents, trastuzumab and ramucirumab, the treatment options for advanced-stage gastric cancer are limited. Consequently, the overall clinical outcomes for patients with advanced-stage gastric cancer remain poor. Numerous agents that are active against novel targets have been evaluated in the course of randomized trials; however, most have produced disappointing results because of the molecular heterogeneity of gastric cancer. The Cancer Genome Atlas (TCGA) project proposed a new classification system for gastric cancer that includes four different tumor subtypes based on molecular characteristics. This change led to the identification of several distinct and potentially targetable pathways. However, most agents targeting these pathways do not elicit any meaningful clinical benefit when employed for the treatment of advanced-stage gastric cancer. Most advanced-stage gastric cancer trials currently focus on agents that modulate tumor microenvironments and cancer cell stemness. In this review, we summarize data regarding novel compounds that have shown efficacy in early phase studies and show promise as effective therapeutic agents, with special emphasis on those for which phase III trials are either planned or underway.

Chemotherapy-induced peripheral neuropathy—part 2: focus on the prevention of oxaliplatin-induced neurotoxicity

“…Hence, it was suggested that MMP9 mAb has therapeutic potential for the treatment of CIPN. Importantly, a humanized MMP9 antibody (andecaliximab) has reached advanced clinical trials for the treatment of colitis (ClinicalTrials.gov: NCT02405442) [139,140] and alimentary tract cancer (ClinicalTrials.gov: NCT01803282) [141,142]; hence, it may also be repurposed for CIPN [143].…”

Translating Biomarkers of Cholangiocarcinoma for Theranosis: A Systematic Review

“…MMP9 upregulation and its negative association with prognosis in cancers such as gastric cancer has been reported and a monoclonal antibody aimed at MMP9 inhibition is currently in human trials [ 68 ]. A clinical trial commenced in 2016 comparing andecaliximab (also known as GS-5745), which is an MMP9 inhibitor, as monotherapy and in combination with anti-cancer agents in Japanese participants with gastric or gastroesophageal junction adenocarcinoma is currently awaiting results ( , NCT02862535).…”

Chemotherapy-induced necrotising tumour lysis and perforation of a huge gastric cancer simulating emphysematous pancreatitis

“…The current therapeutic approach for stage IV gastric cancer with incurable metastasis aims at volume reduction surgery after adequate chemotherapy probably in combination with targeted or anti-angiogenesis agents [34]. It is exciting to see so many novel therapeutic modalities in development for advanced-stage gastric cancer [35,36]. Nonetheless, based on our experience in this patient, tumour lysis syndrome with severe adverse complications must be taken into consideration when more and more efficient agents are approved for clinical use.…”