Oncogene:PAK4可作为膀胱癌的治疗靶标

2020-04-18 AlexYang MedSci原创

肌层浸润膀胱癌(MIBCs)是具有侵袭性的生殖泌尿系恶性肿瘤。膀胱的转移性尿路上皮癌在目前的化疗下无法治愈,并且能导致早期死亡。之前的研究鉴定了MIBCs的分子亚型,并且对前线疗法具有不同的敏感性,也

肌层浸润膀胱癌(MIBCs)是具有侵袭性的生殖泌尿系恶性肿瘤。膀胱的转移性尿路上皮癌在目前的化疗下无法治愈,并且能导致早期死亡。之前的研究鉴定了MIBCs的分子亚型,并且对前线疗法具有不同的敏感性,也表明了肿瘤异质性的存在。

最近,有研究人员对膀胱癌患者进行了激酶组的多组学分析,从而鉴定治疗靶标。研究发现,在部分膀胱癌(BLCA)中,PAK4存在扩增,过表达和活性升高的情况。通过使用膀胱癌细胞,研究人员确认了PAK4在BLCA细胞增殖和浸润中的作用。更多的是,研究人员观察到一种PAK4抑制剂在减弱BLCA细胞生长中是有效的。PAK4抑制剂和PAK4的RNAi处理下,转录组分析鉴定了另一种激酶-蛋白质酪氨酸激酶6(PTK6)表达升高。激酶抑制剂(vandetanib和dasatinib)组合治疗要比单独使用表现出更强的敏感性。

因此,PAK4在部分MIBC患者(PAK4扩增和/过表达)中也许具有治疗可操作性。他们的结果同样表明了同时抑制PAK4和PTK6也许能克服PAK4的抗性。这些结果仍旧需要在BLCA患者中进行临床调查。

原始出处:

Darshan S. Chandrashekar, Balabhadrapatruni V. S. K. Chakravarthi, Alyncia D. Robinson et al. Therapeutically actionable PAK4 is amplified, overexpressed, and involved in bladder cancer progression. Oncogene. 30 Mar 2020

 

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    2020-10-08 cy0324
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    2020-04-20 zhaojie88
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    2020-04-20 zsyan
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    2020-04-18 留走人康

    膀胱癌真怪,明明是免疫敏感性肿瘤,为什么PD-1治疗效果不好呢?难道靶点不对?将来CD47会不会有效

    0

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