摘要
转移是癌症患者死亡的主要原因:目前尚无有效的癌症转移治疗方法。这主要是由于我们对癌症转移机制的了解不足。越来越多的研究表明,C-X-C基序趋化因子配体12(CXCL12)在各种组织和器官中均过表达。这是一个关键的生态位因子,可以培育转移前的生态位(致瘤土壤),并将肿瘤细胞(致癌的“种子”)募集到这些生态位,从而促进癌细胞的侵袭和转移能力。但是,C-X-C基序趋化因子受体4(CXCR4)在各种癌症干/祖细胞中异常过表达,并充当CXCL12受体。 CXCL12激活CXCR4以及多个下游多个致瘤信号通路,从而促进了多种癌基因的表达。 CXCL12-CXCR4信号轴的激活促进上皮-间质转化(EMT),并使癌症干/祖细胞动员至转移前的生态位。它还可以培养具有高运动性,侵袭性和扩散表型的癌细胞,从而加剧多发性近端或远端癌转移。这导致患者预后不良。基于这一证据,最近的研究探索了靶向CXCL12或CXCR4的抗癌疗法,并在临床前试验中取得了可喜的结果。通过靶向CXCL12-CXCR4信号轴,进一步探索这一新策略及其对转移癌的有效治疗作用,可能会导致一种新颖的疗法,该疗法可以清除肿瘤微环境(“土壤”)并杀死癌细胞,尤其是杀死癌细胞癌症患者中的癌症干/祖细胞(“种子”)。最终,这种方法具有有效治疗转移性癌症的潜力。
关键词: CXCL12,CXCR4,癌症转移,治疗,癌症治疗,信号轴。
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