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下一代测序技术及其在肺癌诊断与治疗中的应用

Next-Generation Sequencing and Applications to the Diagnosis and Treatment of Lung Cancer.

作者信息

Kruglyak Kristina M, Lin Erick, Ong Frank S

机构信息

Oncology, Illumina, Inc., San Diego, CA, USA.

Medical Affairs, Ambry Genetics, Inc., Aliso Viejo, CA, USA.

出版信息

Adv Exp Med Biol. 2016;890:123-36. doi: 10.1007/978-3-319-24932-2_7.

Abstract

Cancer is a genetic disease characterized by uncontrolled growth of abnormal cells. Over time, somatic mutations accumulate in the cells of an individual due to replication errors, chromosome segregation errors, or DNA damage. When not caught by traditional mechanisms, these somatic mutations can lead to cellular proliferation, the hallmark of cancer. Lung cancer is the leading cause of cancer-related mortality in the United States, accounting for approximately 160,000 deaths annually. Five year survival rates for lung cancer remain low (<50 %) for all stages, with even worse prognosis (<15 %) in late stage cases. Technological advances, including advances in next-generation sequencing (NGS), offer the vision of personalized medicine or precision oncology, wherein an individual's treatment can be based on his or her individual molecular profile, rather than on historical population-based medicine. Towards this end, NGS has already been used to identify new biomarker candidates for the early diagnosis of lung cancer and is increasingly used to guide personalized treatment decisions. In this review we will provide a high-level overview of NGS technology and summarize its application to the diagnosis and treatment of lung cancer. We will also describe how NGS can drive advances that bring us closer to precision oncology and discuss some of the technical challenges that will need to be overcome in order to realize this ultimate goal.

摘要

癌症是一种遗传性疾病,其特征是异常细胞不受控制地生长。随着时间的推移,由于复制错误、染色体分离错误或DNA损伤,个体细胞中会积累体细胞突变。当这些体细胞突变未被传统机制捕获时,就会导致细胞增殖,这是癌症的标志。肺癌是美国癌症相关死亡的主要原因,每年约有16万人死亡。肺癌各阶段的五年生存率仍然很低(<50%),晚期病例的预后更差(<15%)。包括下一代测序(NGS)进展在内的技术进步,为个性化医疗或精准肿瘤学带来了愿景,即个人的治疗可以基于其个体分子特征,而不是基于基于历史人群的医学。为此,NGS已被用于识别肺癌早期诊断的新生物标志物候选物,并越来越多地用于指导个性化治疗决策。在本综述中,我们将对NGS技术进行高层次概述,并总结其在肺癌诊断和治疗中的应用。我们还将描述NGS如何推动进展,使我们更接近精准肿瘤学,并讨论为实现这一最终目标需要克服的一些技术挑战。

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