Antibody-based targeted therapy for gastric cancer

Abstract

Systemic chemotherapy has been used to treat gastric cancer in Japan, Europe, and North America since the late 1950s. However, the benefit remained unclear until the 1990s, when several studies revealed a quantifiable improvement of life expectancy and quality of life following chemotherapy in patients with stage IV disease. Unfortunately, prognosis remains very poor in patients with advanced disease. In large-scale, prospectively controlled randomized phase III trials, median survival times for patients with metastatic disease do not generally exceed 10 months [1]. In stage II and III disease, the use of perioperative chemotherapy, and also radiotherapy, is still controversial [2]. One of the key treatment issues is that gastric cancer has limited chemosensitivity. While chemotherapy can result in infrequent complete remissions, partial responses are usually of very short duration and many of the treatment regimens in use are cumbersome to administer and can cause serious side effects. In brief, effective systemic treatment for patients with advanced gastric cancer is currently an unmet need in medical oncology. Over the past few years, research into tumor biology, the cellular and molecular mechanisms responsible for malignant proliferation and tumor spread, and increasing knowledge of specific targets has resulted in the development of surprisingly active anti-tumor drugs. Of these, monoclonal antibodies (mAbs), directed against specific cell-surface antigens or their ligands, represent the most widely used and effective “targeted therapies” in the treatment of malignant tumors. Bevacizumab (Avastin; Genentech, San Francisco, CA, USA), a recombinant humanized mAb targeted against vascular epithelial growth factor (VEGF), is approved for the treatment of metastatic colorectal cancer, based on data showing improved survival when added to chemotherapy [3,4]. Bevacizumab can also augment the activ