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Cancer Res:纳米药物新组合有望解决乳腺癌耐药问题

2016-06-26 佚名 生物谷

近日,来自加拿大多伦多Sunnybrook研究所的研究人员在国际学术期刊Cancer Research上发表了一项最新研究进展,他们发现将一种纳米颗粒化疗药物与抗血管生成药物联合使用能够有效治疗乳腺癌。 将bevacizumab等靶向VEGF信号途径的抗血管生成药物与化疗药物结合使用改变了对多种人类乳腺癌的临床治疗实践。但是在治疗过程中经常会产生适应性耐药,其中一个主要机制在于肿瘤内部低氧环境

近日,来自加拿大多伦多Sunnybrook研究所的研究人员在国际学术期刊Cancer Research上发表了一项最新研究进展,他们发现将一种纳米颗粒化疗药物与抗血管生成药物联合使用能够有效治疗乳腺癌

将bevacizumab等靶向VEGF信号途径的抗血管生成药物与化疗药物结合使用改变了对多种人类乳腺癌的临床治疗实践。但是在治疗过程中经常会产生适应性耐药,其中一个主要机制在于肿瘤内部低氧环境的产生以及抗血管生成药物造成的HIF-1a表达上调。进行抗血管生成治疗之后虽然肿瘤内部血管数目减少血管功能受到抑制,但是会影响化疗药物向肿瘤内部的输送。

与bevacizumab联合使用的化疗药物不仅应该能够降低HIF1a水平克服低氧诱导的适应性抵抗,同时还应该提高肿瘤灌注维持药物向肿瘤内部的输送。

在这项研究中,研究人员利用人类来源肿瘤异种移植动物(PDX)等临床前小鼠模型评估了bevacizumab以及一种包含喜树碱的纳米颗粒药物(CRLX101)对三阴性乳腺癌的治疗效果,还评估了这两种药物对手术后晚期转移性乳腺癌小鼠的长期治疗效果。

研究结果表明CRLX101单独使用以及与bevacizumab联用都非常有效,都能导致肿瘤发生退化,抑制肿瘤转移并能够大大延长转移性癌症小鼠模型生存时间。除此之外,CRLX101还能够提高肿瘤灌注,改善低氧环境。研究还发现CRLX101能够持续抑制HIF1a,因此或可潜在抵消bevacizumab引起的肿瘤低氧造成的不良影响。

这些临床前结果表明将CRLX101这种具备细胞毒性的强力纳米颗粒化疗药物与抗血管生成药物联合使用或许会成为治疗转移性乳腺癌的一种新策略。

原始出处

Elizabeth Pham, Melissa Yin, Christian G Peters, Christina R. Lee, Donna Brown, Ping Xu, Shan Man, Lata Jayaraman, Ellen Rohde, Annabelle Chow, Douglas Lazarus, Scott Eliasof, F. Stuart Foster, Robert S Kerbel.Preclinical efficacy of bevacizumab with CRLX101, an investigational nanoparticle-drug conjugate, in treatment of metastatic triple-negative breast cancer.Cancer Res.2016

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    2016-06-28 xugc

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