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Nature:新药物靶标可打破癌症抵抗治疗的屏障

  1. FAK
  2. 癌症
  3. 肿瘤

来源:生物谷 2014-07-31 14:53

近日,Barts Cancer Institute科学家发现,靶向血管中的一分子(FAK)可以使癌症治疗显著更有效。

2014年7月29日讯 /生物谷BIOON/--近日,Barts Cancer Institute科学家发现,靶向血管中的一分子(FAK)可以使癌症治疗显著更有效。

研究团队已经发现一种分子粘着斑激酶(FAK)发送信号给肿瘤细胞,从而帮助化疗或放疗(破坏DNA,杀死癌细胞)后的自我修复。当研究人员从黑色素瘤和肺癌模型血管中移除FAK,化疗和放射疗法能更有效地杀死肿瘤。

研究人员还研究了淋巴瘤患者的样本,发现那些血管中FAK低水平的患者,有更好的治疗结果。这表明,开发剔除肿瘤血管FAK的药物,可能促进癌症的治疗和预防癌症复发。

血管内壁细胞向肿瘤发出化学信号(称为细胞因子)以帮助它抵抗DNA损伤和恢复。研究人员证明,这个过程需要FAK,没有FAK,这些信号都不会发送,使肿瘤更容易受到DNA损伤。

这是令人兴奋的研究,我们可能已经破解血管中健康细胞如何防止癌症的治疗的秘密,本研究虽然仅在老鼠模型中完成,但它能提高现有癌症药物的有效性以及癌症对药物的敏感性,这才是真正的希望。(生物谷Bioon.com)

Endothelial-FAK targeting sensitises tumours to DNA-damaging therapy

Bernardo Tavora,  Louise E. Reynolds,  Silvia Batista,  Fevzi Demircioglu,  Isabelle Fernandez,  Tanguy Lechertier,  Delphine M. Lees,  Ping-Pui Wong,  Annika Alexopoulou, George Elia,  Andrew Clear,  Adeline Ledoux,  Jill Hunter,  Neil Perkins,  John G. Gribben  & Kairbaan M. Hodivala-Dilke

Chemoresistance is a serious limitation of cancer treatment1. Until recently, almost all the work done to study this limitation has been restricted to tumour cells2. Here we identify a novel molecular mechanism by which endothelial cells regulate chemosensitivity. We establish that specific targeting of focal adhesion kinase (FAK; also known as PTK2) in endothelial cells is sufficient to induce tumour-cell sensitization to DNA-damaging therapies and thus inhibit tumour growth in mice. The clinical relevance of this work is supported by our observations that low blood vessel FAK expression is associated with complete remission in human lymphoma. Our study shows that deletion of FAK in endothelial cells has no apparent effect on blood vessel function per se, but induces increased apoptosis and decreased proliferation within perivascular tumour-cell compartments of doxorubicin- and radiotherapy-treated mice. Mechanistically, we demonstrate that endothelial-cell FAK is required for DNA-damage-induced NF-κB activation in vivo and in vitro, and the production of cytokines from endothelial cells. Moreover, loss of endothelial-cell FAK reduces DNA-damage-induced cytokine production, thus enhancing chemosensitization of tumour cells to DNA-damaging therapies in vitro and in vivo. Overall, our data identify endothelial-cell FAK as a regulator of tumour chemosensitivity. Furthermore, we anticipate that this proof-of-principle data will be a starting point for the development of new possible strategies to regulate chemosensitization by targeting endothelial-cell FAK specifically.

 

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