Monoclonal antibodies-based treatment in gastric cancer: current status and future perspectives

Abstract

Gastric cancer (GC) is the second leading cause of cancer-related death, and despite having improved treatment modalities over the last decade, for most patients, only modest improvements have been seen in overall survival. Recent progress in understanding the molecular biology of GC and the related signaling pathways offers, from the clinical point of view, promising advances for selected groups of patients. In the past, targeted therapies have significantly impacted the treatment strategy of several common solid tumors such as breast, colorectal, and lung cancers. Unfortunately, translational and clinical research shows fewer encouraging targeted treatments with regards to the GC. To date, only two monoclonal antibodies (mAb), named trastuzumab and ramucirumab, are approved for the treatment of advanced GC, suggesting that in GC, maybe more than in other cancers, effective targeted therapy requires patient selection based on precise predictive molecular biomarkers. The aim of this review is to summarize the available data on the clinical advantages offered by the use of mAbs in the treatment of advanced/metastatic GC. Future perspective is also discussed.

Inhibition or Reversal of the Epithelial-Mesenchymal Transition in Gastric Cancer: Pharmacological Approaches

“…Except for ramucirumab, bevacizumab, another anti-VEGF antibody, might be applied to treat GC by inhibiting angiogenesis. To prevent pathological angiogenesis in the GC microenvironment, anti-EGFR agents such as cetuximab, panitumumab, or matuzumab can also be used [223].…”

Docetaxel, oxaliplatin, 5FU, and trastuzumab as first-line therapy in patients with human epidermal receptor 2-positive advanced gastric or gastroesophageal junction cancer

“…Trastuzumab is a humanized recombinant monoclonal antibody that selectively binds to the extracellular domain of human epidermal receptor 2 (HER2). [ 7 ] The trastuzumab for gastric cancer (ToGA) trial evaluated the combination of trastuzumab with a cisplatin/fluoropyrimidine chemotherapy doublet in patients with previously untreated advanced HER2-positive gastroesophageal cancer [ 8 ] showing a survival benefit. However, little data are available on efficacy and toxicity of a triplet taxane-based regimen chemotherapy for HER2-positive gastroesophageal tumors.…”

Apatinib for the treatment of gastric cancer

“…Nonetheless, apatinib compared to placebo has been shown to improve overall survival, progression free survival and response rate in heavily pre-treated patients (i.e. those Approval was based on gains in overall survival when the drug was administered either alone or in combination with paclitaxel in phase III studies [11]. Of note, although ramucirumab and apatinib target the same signalling pathway, they have different mechanisms of action.…”