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靶向ALK相关癌症中的自噬

Targeting Autophagy in ALK-Associated Cancers.

作者信息

Frentzel Julie, Sorrentino Domenico, Giuriato Sylvie

机构信息

Merck Serono S.A., Route de Fenil 25, Z.I. B, 1804 Corsier-sur-Vevey, Switzerland.

Inserm, UMR1037, CNRS, ERL5294, Université Toulouse III-Paul Sabatier, CRCT, F-31000 Toulouse, France.

出版信息

Cancers (Basel). 2017 Nov 27;9(12):161. doi: 10.3390/cancers9120161.

Abstract

Autophagy is an evolutionarily conserved catabolic process, which is used by the cells for cytoplasmic quality control. This process is induced following different kinds of stresses e.g., metabolic, environmental, or therapeutic, and acts, in this framework, as a cell survival mechanism. However, under certain circumstances, autophagy has been associated with cell death. This duality has been extensively reported in solid and hematological cancers, and has been observed during both tumor development and cancer therapy. As autophagy plays a critical role at the crossroads between cell survival and cell death, its involvement and therapeutic modulation (either activation or inhibition) are currently intensively studied in cancer biology, to improve treatments and patient outcomes. Over the last few years, studies have demonstrated the occurrence of autophagy in different Anaplastic Lymphoma Kinase (ALK)-associated cancers, notably ALK-positive anaplastic large cell lymphoma (ALCL), non-small cell lung carcinoma (NSCLC), Neuroblastoma (NB), and Rhabdomyosarcoma (RMS). In this review, we will first briefly describe the autophagic process and how it can lead to opposite outcomes in anti-cancer therapies, and we will then focus on what is currently known regarding autophagy in ALK-associated cancers.

摘要

自噬是一种进化上保守的分解代谢过程,细胞利用它进行细胞质质量控制。该过程在诸如代谢、环境或治疗等不同类型的应激后被诱导,并在此框架内作为一种细胞存活机制发挥作用。然而,在某些情况下,自噬与细胞死亡有关。这种双重性在实体癌和血液系统癌症中已有广泛报道,并且在肿瘤发生发展和癌症治疗过程中均有观察到。由于自噬在细胞存活和细胞死亡的交叉点上起着关键作用,目前在癌症生物学领域对其参与情况和治疗调节(激活或抑制)进行了深入研究,以改善治疗效果和患者预后。在过去几年中,研究已经证明自噬在不同的间变性淋巴瘤激酶(ALK)相关癌症中存在,特别是ALK阳性间变性大细胞淋巴瘤(ALCL)、非小细胞肺癌(NSCLC)、神经母细胞瘤(NB)和横纹肌肉瘤(RMS)。在本综述中,我们将首先简要描述自噬过程以及它在抗癌治疗中如何导致相反的结果,然后我们将重点关注目前关于ALK相关癌症中自噬的已知情况。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9702/5742809/c87490bc414b/cancers-09-00161-g001.jpg

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