Title:Targeted Therapy in Advanced Gastric Carcinoma: The Future is Beginning
Volume: 21
Issue: 8
Author(s): G. Schinzari, A. Cassano, A. Orlandi, M. Basso and C. Barone
Affiliation:
Keywords:
c-MET, EGFR, gastric cancer, HER-2, mTOR, VEGF.
Abstract: Gastric cancer represents one of the most common cancer worldwide. Unfortunately, the majority of patients
present in advanced stage and outcome still remains poor with high mortality rate despite decreasing incidence and new
diagnostic and therapeutic strategies. Although utility of classical chemotherapy agents has been widely explored, advances
have been slow and the efficacy of these agents has reached a plateau of median overall survival not higher than 12
months. Therefore, researchers focused their attention on better understanding molecular biology of carcinogenesis and
deeper knowledge of the cancer cell phenotype, as well on development of rationally designed drugs that would target
specific molecular aberrancies in signal transduction pathways. These targets include cell surface receptors, circulating
growth and angiogenic factors and other molecules involved in downstream intracellular signaling pathways, including
receptor tyrosine kinases. However, therapeutic advances in gastric cancer are not so encouraging when compared to other
solid organ malignancies such as breast and colorectal cancer. This article reviews the role of targeted agents in gastric
cancer as single-agent therapy or in combination regimens, including their rational and emerging mechanism of action,
current and emerging data. We focused our attention mainly on published phase III studies, therefore cornerstone clinical
trials with trastuzumab and bevacizumab have been largely discussed. Phase III studies presented in important international
meetings are also reviewed as well phase II published studies and promising new therapies investigated in preclinical
or phase I studies. Today, in first-line treatment only trastuzumab has shown significantly increased survival in combination
with chemotherapy, whereas ramucirumab as single agent resulted effective in progressing patients, but - despite
several disappointing results - these are the proof of principle that targeting the proper molecular aberration is the best
way for implementing outcome of therapy.
