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.

The Chemokine Receptor CXCR4 and c-MET Cooperatively Promote Epithelial-Mesenchymal Transition in Gastric Cancer Cells

“…Moreover, its receptor, C-X-C motif chemokine receptor 4 (CXCR4), is a G protein–coupled receptor (GPCR) that has been detected in more than 20 solid tumor types, making it one of the most frequently overexpressed chemokine receptors in malignancy [2] , [3] . Drugs targeting the CXCL12/CXCR4 axis can inhibit tumor growth and metastasis in animal models [4] , [5] . Therefore, targeting this pathway might be a promising new therapeutic strategy.…”

Evaluation of the mechanisms and effects of Mg–Ag–Y alloy on the tumor growth and metastasis of the MG63 osteosarcoma cell line

“…CXCR4 is a seven transmembrane spanning receptor type of protein and it plays an important role in tumor metastasis. Importantly, the metastasis incidence of CXCR4‐overexpressing tumor is significantly increased . In this study, we selected AKP and CXCR4 to respectively evaluate cell viability and tumor metastatic potential.…”

Ping-Pong—Tumor and Host in Pancreatic Cancer Progression

“…Great progress over the last decade extended original findings toward the involvement of tumor stroma and EC. Although the extent of CXCR4 heterocomplex engagement in leukocyte recruitment awaits further exploration (364), based on promising results, great efforts are taken toward therapeutic translation (100,365,366).…”