Metastatic gastric cancer - focus on targeted therapies

Abstract

Gastric cancer (GC) is currently the second leading cause of cancer death worldwide; unfortunately, most patients will present with locally advanced or metastatic disease. Despite recent progress in diagnosis, surgery, chemotherapy, and radiotherapy, prognosis remains poor. A better understanding of GC biology and signaling pathways is expected to improve GC therapy, and the integration of targeted therapies has recently become possible and appears to be promising. This article focuses on anti-Her-2 therapy, specifically trastuzumab, as well as other epidermal growth factor receptor antagonists such as cetuximab, panitumub, matuzumab, nimotzumab, gefitinib, and erlotinib. Additionally, drugs that target angiogenesis pathways are also under investigation, particulary bevacizumab, ramucirumab, sorafenib, sunitinib, and cediranib. Other targeted agents in preclinical or early clinical development include mTOR inhibitors, anti c-MET, polo-like kinase 1 inhibitors, anti-insulin-like growth factor, anti-heat shock proteins, and small molecules targeting Hedgehog signaling.

Keywords: anti-EGFR drugs; antiangiogenesis drugs; gastric cancer; targeted therapy.

Figure 1

Relevant anti VEGF pathways therapies in advanced gastric cancer. Abbreviations: VEGF, vascular endothelial growth factor; VEGFR, vascular endothelial growth factor receptor; PGF, placenta growth factor.

Figure 2

Molecular targets and relevant drugs (anti-EGFR/Her-2) in advanced gastric cancer. Abbreviations: AKT, protein kinase B; MAPK, mitogen-activated protein kinase; MEK, MAP kinase kinase; mTOR 1&2, mammalian target of rapamycin 1&2; PI3K, phosphatidylinositol 3 kinase; Raf, GTPase Raf; Ras, GTPase Ras; SOS, son of sevenless homolog.