Translating an Antagonist of Chemokine Receptor CXCR4: from bench to bedside.
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.
Wong
Donald
D
Chemokine Therapeutics Corporation, Vancouver, British Columbia, Canada. reprint@chemokine.net
Korz
Walter
W
D054377:Chemokine CXCL12 / Q000502:physiology; D006801:Humans; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors* / Q000502:physiology; D015398:Signal Transduction
C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D019718:Receptors, CXCR4