Targeting receptor tyrosine kinases in gastric cancer.
Molecularly targeted therapeutic agents are constantly being developed and have been shown to be effective in various clinical trials. One group of representative targeted oncogenic kinases, the receptor tyrosine kinases (RTKs), has been associated with gastric cancer development. Trastuzumab, an inhibitor of ERBB2, has been approved for the treatment of gastric cancer, although other receptor tyrosine kinases, such as epidermal growth factor receptor, vascular endothelial growth factor, platelet-derived growth factor receptor, c-Met, IGF-1R and fibroblast growth factor receptor 2, are also activated in gastric cancer. The promising results of the trastuzumab clinical trial for gastric cancer resulted in the approval of trastuzumab-based therapy as a first-line treatment for human epidermal growth factor receptor 2-positive patients. On the other hand, the trial examining bevacizumab in combination with conventional chemotherapy did not meet its primary goal of increasing the overall survival time of gastric cancer patients; however, a significantly higher response rate and a longer progression-free survival were observed in the bevacizumab arm of the trial. Other clinical trials, especially phase III trials that have tested drugs targeting RTKs, such as cetuximab, panitumumab, gefitinib, erlotinib, figitumumab, sorafenib, sunitinib and lapatinib, have shown that these drugs have modest effects against gastric cancer. This review summarizes the recent results from the clinical trials of molecularly targeted drugs and suggests that further improvements in the treatment of advanced gastric cancer can be achieved through the combination of conventional drugs with the new molecularly targeted therapies.
Asahiro Morishita, Jian Gong, Tsutomu Masaki, Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Kagawa 761-0793, Japan.
Asahiro
A
Morishita
Asahiro Morishita, Jian Gong, Tsutomu Masaki, Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Kagawa 761-0793, Japan.
Jian
J
Gong
Asahiro Morishita, Jian Gong, Tsutomu Masaki, Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Kagawa 761-0793, Japan.
Tsutomu
T
Masaki
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018450:Disease Progression; D018572:Disease-Free Survival; D006801:Humans; D058990:Molecular Targeted Therapy; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality / Q000473:pathology; D013997:Time Factors; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases
Bevacizumab; Cetuximab; Epidermal growth factor receptor; Erlotinib; Gastric cancer; Lapatinib; Panitumumab; Receptor tyrosine kinases; Trastuzumab