Inhibition of CXCL12/CXCR4 axis as a potential targeted therapy of advanced gastric carcinoma

Cancer Med. 2017 Jun;6(6):1424-1436. doi: 10.1002/cam4.1085. Epub 2017 May 23.

Abstract

The whole outcome for patients with gastric carcinoma (GC) is very poor because most of them remain metastatic disease during survival even at diagnosis or after surgery. Despite many improvements in multiple strategies of chemotherapy, immunotherapy, and targeted therapy, exploration of novel alternative therapeutic targets is still warranted. Chemokine receptor 4 (CXCR4) and its chemokine ligand 12 (CXCL12) have been identified with significantly elevated levels in various malignancies including GC, which correlates with the survival, proliferation, angiogenesis, and metastasis of tumor cells. Increasing experimental evidence suggests an implication of inhibition of CXCL12/CXCR4 axis as a promising targeted therapy, although there are rare trials focused on the therapeutic efficacy of CXCR4 inhibitors in GC until recently. Therefore, it is reasonable to infer that specific antagonists or antibodies targeting CXCL12/CXCR4 axis alone or combined with chemotherapy will be effective and worthy of further translational studies as a potential treatment strategy in advanced GC.

Keywords: CXCL12; CXCR4; CXCR7; gastric carcinoma; inhibitor; targeted therapy.

Publication types

  • Review

MeSH terms

  • Animals
  • Chemokine CXCL12 / antagonists & inhibitors*
  • Chemokine CXCL12 / metabolism
  • Humans
  • Molecular Targeted Therapy
  • Receptors, CXCR4 / antagonists & inhibitors*
  • Receptors, CXCR4 / metabolism
  • Signal Transduction
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology

Substances

  • CXCL12 protein, human
  • CXCR4 protein, human
  • Chemokine CXCL12
  • Receptors, CXCR4