Molecular basis of therapeutic approaches to gastric cancer.
Gastric cancer is the top lethal cancer in Asia. As the majority of cases present with advanced disease, conventional therapies (surgery, chemotherapy, and radiotherapy) have limited efficacy to reduce mortality. Emerging modalities provide promise to combat this malignancy. Target-protein-based cancer therapy has become available in clinical practice. Numerous molecules have been shown potential to target specific pathways for tumor cell growth. Cyclooxygenase-2 (COX-2) is overexpressed in and correlated with gastric cancer, and knockdown of COX-2 or administration of COX-2 inhibitors suppresses tumor formation in models of gastric cancer. Induction of apoptosis, reduction of angiogenesis, and blocking of potassium ion channels may present new mechanisms of COX-2 inhibition. Runt-related transcription factor 3 (RUNX3) is a candidate tumor suppressor gene whose deficiency is causally related to gastric cancer. RUNX3 is downregulated in metastatic gastric cancer. RUNX3 activation inhibits angiogenesis in xenograft tumors in nude mice. Tumor microenvironment modulation also provides a powerful tool to inhibit cancer development and progress; details of the potential roles of angiopoietins are discussed in this review. Osteopontin is a secreted protein involved in stress response, inflammation, wound healing, and immune response. Inhibition of osteopontin by RNA interfering technique suppressed tumorigenesis as well as angiogenesis in gastric cancer. Immunotherapy remains another important choice of adjuvant therapy for cancer. A tumor-specific antigen MG7-Ag has been identified with great potential for inducing immune response in gastric cancer. Using HLA-A-matched allogeneic gastric cancer cells to induce tumor-specific cytotoxic T lymphocytes appeared to be an alternative option of immunotherapy for gastric cancer.
Wu
Kaichun
K
State Key Laboratory of Cancer Biology and Institute of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China. kaicwu@fmmu.edu.cn
Nie
Yongzhan
Y
Guo
Changcun
C
Chen
Yu
Y
Ding
Jie
J
Fan
Daiming
D
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D042501:Angiogenic Proteins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use*; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use; D015195:Drug Design; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D026902:Potassium Channel Blockers / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000627:therapeutic use; D013274:Stomach Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000628:therapy*
D020533:Angiogenesis Inhibitors; D042501:Angiogenic Proteins; D000970:Antineoplastic Agents; D050677:Core Binding Factor Alpha 3 Subunit; D052246:Cyclooxygenase 2 Inhibitors; D026902:Potassium Channel Blockers; D047428:Protein Kinase Inhibitors; D034741:RNA, Small Interfering; C493729:Runx3 protein, human; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human