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Translating an Antagonist of Chemokine Receptor CXCR4: From Bench to Bedside

Authors' Affiliation: Chemokine Therapeutics Corporation, Vancouver, British Columbia, Canada

Requests for reprints: Donald Wong, Chemokine Therapeutics Corporation, Suite 400, 1727 West Broadway, Vancouver, British Columbia, Canada V6J 4S5. E-mail: reprint{at}chemokine.net.

Abstract

The majority of current cancer therapies focus on a primary tumor approach. However, it is metastases that cause the majority of cancer deaths. The metastatic process has been shown repeatedly to be greatly influenced by chemokines such as CXCL12 [stromal cell derived factor-1 (SDF-1)] and its receptor CXCR4. The activation of this pathway has been reported to modulate cell migration, survival, proliferation, and gene transcription through G proteins, phosphoinositide-3 kinase, Akt, extracellular signal-regulated kinase, arrestin, and Janus-activated kinase/signal transducers and activators of transcription. A wide variety of strategies, such as peptides, small molecules, antibodies, and small interfering RNA, have been used to target this pathway. Treatments in combination with current therapies seem to be especially promising in preclinical studies. A few compounds are advancing into early stages of clinical development. In this article, we will review the development of CXCR4 antagonists in oncology.

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