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

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.

Chemokine receptor 4 (CXCR4) and its chemokine ligand 12 (CXCL12) have been identified with significantly increased levels in various malignancies including gastric carcinoma (GC), which correlates with the survival, proliferation, angiogenesis, and metastasis of tumor cells. Increasing experimental evidence suggest an implication of inhibition of CXCL12/CXCR4 axis as a promising targeted therapy, although there are rare studies focused on the therapeutic efficacy of CXCR4 inhibitors in GC until recently. This review therefore aims to summarize and discuss multiple biological roles of CXCL12/CXCR4 axis and the potential application of CXCR4 inhibitors as a targeted therapy in advanced GC.

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