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乳腺癌中蛋白质复合物的治疗及作用机制展望

Therapeutic and Mechanistic Perspectives of Protein Complexes in Breast Cancer.

作者信息

Waterhouse Mark P, Ugur Rosie, Khaled Walid T

机构信息

Department of Pharmacology, University of Cambridge, Cambridge, United Kingdom.

出版信息

Front Cell Dev Biol. 2019 Dec 20;7:335. doi: 10.3389/fcell.2019.00335. eCollection 2019.

Abstract

Breast cancer affects one in eight women making it the most common cancer in the United Kingdom, accounting for 15% of all new cancer cases. One of the main challenges in treating breast cancer is the heterogeneous nature of the disease. At present, targeted therapies are available for hormone receptor- and HER2-positive tumors. However, no targeted therapies are currently available for patients with triple negative breast cancer (TNBC). This likely contributes to the poor prognostic outcome for TNBC patients. Consequently, there is a clear clinical need for the development of novel drugs that efficiently target TNBC. Extensive genomic and transcriptomic characterization of TNBC has in recent years identified a plethora of putative oncogenes. However, these driver oncogenes are often critical in other cell types and/or transcription factors making them very difficult to target directly. Therefore, other approaches may be required for developing novel therapeutics that fully exploit the specific functions of TNBC oncogenes in tumor cells. Here, we will argue that more research is needed to identify the protein-protein interactions of TNBC oncogenes as a means for (a) mechanistically understanding the biological function of these oncogenes in TNBC and (b) providing novel therapeutic targets that can be exploited for selectively inhibiting the oncogenic roles of TNBC oncogenes in cancer cells, whilst sparing normal healthy cells.

摘要

乳腺癌影响着八分之一的女性,使其成为英国最常见的癌症,占所有新发癌症病例的15%。治疗乳腺癌的主要挑战之一是该疾病的异质性。目前,针对激素受体阳性和HER2阳性肿瘤有靶向疗法。然而,目前三阴性乳腺癌(TNBC)患者尚无靶向疗法。这可能是TNBC患者预后不良的原因。因此,临床上显然需要开发能够有效靶向TNBC的新型药物。近年来,对TNBC进行的广泛基因组和转录组特征分析发现了大量假定的致癌基因。然而,这些驱动致癌基因在其他细胞类型和/或转录因子中往往也很关键,这使得它们很难直接成为靶点。因此,可能需要其他方法来开发新型疗法,以充分利用TNBC致癌基因在肿瘤细胞中的特定功能。在此,我们认为需要更多研究来确定TNBC致癌基因的蛋白质-蛋白质相互作用,以此作为(a)从机制上理解这些致癌基因在TNBC中的生物学功能,以及(b)提供可用于选择性抑制TNBC致癌基因在癌细胞中的致癌作用,同时保护正常健康细胞的新型治疗靶点的一种手段。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7834/6932950/4b40c640736d/fcell-07-00335-g001.jpg

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