CXCL12-CXCR4在人类恶性肿瘤中的生物学功能

转移和细胞浸润是实体癌和淋巴癌治疗的难点,也是疾病复发和死亡的主要原因。癌细胞的迁移是肿瘤转移和侵袭的前提。CXCL12-CXCR4通路在实体瘤和白血病的发病中发挥重要作用。CXCL12与其受体CXCR4之间的相互作用可以激活多种信号通路,调节不同的生理和病理生理过程。因此,阻断CXCL12-CXCR4的结合和/或下游通路在治疗各种疾病和癌症方面具有临床益处。目前,已发现一些CXCL12和CXCR4拮抗剂,并通过研究证实其在抗肿瘤活性方面取得了令人鼓舞的结果;但这些药物由于其严重的毒副作用未能大规模应用于临床患者。迫切需要研发新型CXCL12-CXCR4轴拮抗剂以治疗肿瘤。本文综述了CXCR4通路在实体肿瘤和白血病中的最新研究进展,并讨论了CXCR4通路在实体肿瘤和白血病中的治疗价值和未来的研究方向。

Biological Functions of CXCL12-CXCR4 in Human Malignant Tumors

Metastasis and cell infiltration are the difficulties in the treatment of solid and lymphatic carcinoma and the main causes of disease recurrence and death. The migration of cancer cells is a prerequisite for tumor metastasis and invasion. The CXCL12-CXCR4 pathway plays an important role in the pathogenesis of solid tumors and leukemia. The interaction between CXCL12 and its receptor CXCR4 can activate multiple signaling pathways and regulate different physiological and pathophysiological processes. Thus, blocking CXCL12-CXCR4 binding and/or downstream pathways has clinical benefits in treating a variety of diseases and cancers. Although some CXCL12 and CXCR4 antagonists have been identified and have shown encouraging results in terms of antitumor activity, these drugs have not been widely used in clinical patients due to their serious toxic and side effects. There is an urgent need to develop novel CXCL12-CXCR4 axis antagonists for the treatment of tumors. Herein, we review the recent research progress of CXCR4 pathway in solid tumors and leukemia, and discuss the therapeutic value and future research direction of CXCR4 pathways in solid tumors and leukemia.