Therapeutics target of CXCR4 and its downstream in peritoneal carcinomatosis of gastric cancer.
Patients with advanced gastric carcinoma, especially peritoneal dissemination, have a poor prognosis. Various treatments have been used for peritoneal dissemination of gastric cancer, but there is no effective therapy for this condition. At present, similar proprieties of chemokines between trafficking of leukocytes during immune and inflammatory reactions and organ selective migration of cancer cells during metastasis are widely recognized. In particular, chemokine CXCL12 and its receptors CXCR4 are now known to play an important role in cancer progression. Recently, we reported for the first time that CXCR4 and its ligand, CXCL12, were involved in the development of peritoneal carcinomatosis of gastric cancer, and additionally, clarified the molecular mechanisms of the cell signaling pathways by which gastric cancer develops metastatic ability via CXCR4 and mTOR. In this review, we focus on the biological functions of chemokine receptors, particularly CXCR4 expressed on gastric cancer cells, and the therapeutic strategies targeting CXCR4-mediating signaling pathways in peritoneal carcinomatosis.
Division of Kampo Diagnostics, Institute of Natural Medicine, University of Toyama, Toyama, Japan. kkoizumi@inm.u-toyama.ac.jp
Keiichi
K
Koizumi
Shinichiro
S
Kato
Hiroaki
H
Sakurai
Isaya
I
Hashimoto
Kazuo
K
Yasumoto
Ikuo
I
Saiki
D000818:Animals; D002277:Carcinoma / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D054377:Chemokine CXCL12 / Q000378:metabolism; D006801:Humans; D058990:Molecular Targeted Therapy; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology
D054377:Chemokine CXCL12; D019718:Receptors, CXCR4