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肺癌的分子组织学:从靶点到治疗。

Molecular histology of lung cancer: from targets to treatments.

机构信息

Faculty Institute of Cancer Sciences, University of Manchester, Manchester Academic Health Science Centre, Wolfson Molecular Imaging Centre, Manchester M20 3LJ, UK.

Faculty Institute of Cancer Sciences, University of Manchester, Manchester Academic Health Science Centre, Wolfson Molecular Imaging Centre, Manchester M20 3LJ, UK; Karolinska Institutet, Department of Oncology and Pathology, SciLifeLab, Tomtebodavägen 23A, 17165 Solna, Sweden.

出版信息

Cancer Treat Rev. 2015 Apr;41(4):361-75. doi: 10.1016/j.ctrv.2015.02.008. Epub 2015 Feb 20.

Abstract

Lung cancer is the leading cause of cancer-related death worldwide with a 5-year survival rate of less than 15%, despite significant advances in both diagnostic and therapeutic approaches. Combined genomic and transcriptomic sequencing studies have identified numerous genetic driver mutations that are responsible for the development of lung cancer. In addition, molecular profiling studies identify gene products and their mutations which predict tumour responses to targeted therapies such as protein tyrosine kinase inhibitors and also can offer explanation for drug resistance mechanisms. The profiling of circulating micro-RNAs has also provided an ability to discriminate patients in terms of prognosis/diagnosis and high-throughput DNA sequencing strategies are beginning to elucidate cell signalling pathway mutations associated with oncogenesis, including potential stem cell associated pathways, offering the promise that future therapies may target this sub-population, preventing disease relapse post treatment and improving patient survival. This review provides an assessment of molecular profiling within lung cancer concerning molecular mechanisms, treatment options and disease-progression. Current areas of development within lung cancer profiling are discussed (i.e. profiling of circulating tumour cells) and future challenges for lung cancer treatment addressed such as detection of micro-metastases and cancer stem cells.

摘要

肺癌是全球癌症相关死亡的主要原因,尽管在诊断和治疗方法上都取得了重大进展,但 5 年生存率仍低于 15%。联合基因组和转录组测序研究已经确定了许多导致肺癌发生的遗传驱动突变。此外,分子谱分析鉴定了基因产物及其突变,这些突变可预测肿瘤对靶向治疗(如蛋白酪氨酸激酶抑制剂)的反应,还可以解释耐药机制。循环 microRNA 的分析也提供了区分患者预后/诊断的能力,高通量 DNA 测序策略开始阐明与肿瘤发生相关的细胞信号通路突变,包括潜在的与干细胞相关的途径,这有望使未来的治疗方法能够针对这一亚群,防止治疗后疾病复发并提高患者生存率。本文就肺癌的分子谱分析在分子机制、治疗选择和疾病进展方面进行了评估。讨论了肺癌谱分析的当前发展领域(如循环肿瘤细胞的分析)以及肺癌治疗的未来挑战,如微小转移和癌症干细胞的检测。

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