Sci Tran Med:科学家发现治疗乳腺癌失败的又一大因素

2018-03-15 白木清水 来宝网

肥胖--已知会降低几种癌症的存活率,可能解释了血管生成抑制剂在治疗乳腺癌方面的无效性。一个研究小组首次发现,肥胖和肥胖相关的分子因素似乎在乳腺癌患者和两种小鼠模型中诱导了对抗血管生成治疗的抗性。 他们在“科学转化医学”中的报告还详细介绍了与这种耐药相关的特定肥胖相关因素,并概述了可能会克服它的潜在治疗策略。

肥胖--已知会降低几种癌症的存活率,可能解释了血管生成抑制剂在治疗乳腺癌方面的无效性。一个研究小组首次发现,肥胖和肥胖相关的分子因素似乎在乳腺癌患者和两种小鼠模型中诱导了对抗血管生成治疗的抗性。 他们在“科学转化医学”中的报告还详细介绍了与这种耐药相关的特定肥胖相关因素,并概述了可能会克服它的潜在治疗策略。

“总体而言,我们的临床临床前研究结果表明,根据癌症亚型的不同,肥胖会通过产生几种炎症和促血管生成因子,促进乳腺癌抗血管内皮生长因子治疗的耐药性,”Joao Incio博士说。 “针对这些阻力因素可能会在乳腺癌治疗中重新使用抗血管生成疗法。”

近70%的乳腺癌患者在诊断时超重或肥胖,已知乳腺肿瘤含有相当大比例的脂肪组织。除了VEGF之外,肥胖还与炎症和血管生成因子的水平增加有关,其可以促成抗VEGF抗性。目前的研究旨在通过增加这些因子的产生来研究肥胖促进抗乳腺癌抗VEGF治疗的假设。

该研究小组首先分析了99例乳腺癌患者贝伐单抗的临床试验数据,首先是单独治疗,然后是化疗,这表明抗vegf治疗只对一小部分患者有益。研究人员发现,身体质量指数(BMI)为25或以上的参与者(BMI)为超重或肥胖的患者,其诊断结果比BMI低于25的患者平均高出33%。

此外,体内脂肪含量较高的患者的肿瘤样本的血管供应减少,这可能会干扰对化疗的反应。白细胞介素6 (IL-6)、促炎性分子和成纤维细胞生长因子2 (FGF-2)是一种促血管生成分子,在高BMIs患者中升高,这些因素在脂肪细胞(脂肪细胞)和肿瘤周围的其他细胞中表达。

在两种小鼠乳腺癌模型中进行了多项实验,其中一种是雌激素受体(ER)阳性的癌症,另一种是三阴性的癌症——支持了这些临床研究结果的意义。

原始出处:

Joao Incio, Jennifer A. Ligibel, Daniel T. McManus, et al. Obesity promotes resistance to anti-VEGF therapy in breast cancer by up-regulating IL-6 and potentially FGF-2. Science Translational Medicine (2018).

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    2019-01-29 bsmagic9140
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    2018-03-15 131****2916

    不错的文章值得推荐

    0

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    2018-03-15 有备才能无患

    肥胖--已知会降低几种癌症的存活率.可能解释了血管生成抑制剂在治疗乳腺癌方面的无效性.一个研究小组首次发现.肥胖和肥胖相关的分子因素似乎在乳腺癌患者和两种小鼠模型中诱导了对抗血管生成治疗的抗性.

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    2018-03-15 1e1b8538m79(暂无匿称)

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