Kalita-de Croft Priyakshi, Al-Ejeh Fares, McCart Reed Amy E, Saunus Jodi M, Lakhani Sunil R
*UQ Centre for Clinical Research, The Royal Brisbane & Women's Hospital §School of Medicine, The University of Queensland †QIMR Berghofer Medical Research Institute ‡Pathology Queensland, Royal Brisbane Women's Hospital, Herston, Qld, Australia.
Adv Anat Pathol. 2016 Nov;23(6):356-367. doi: 10.1097/PAP.0000000000000128.
Our understanding of the natural history of breast cancer has evolved alongside technologies to study its genomic, transcriptomic, proteomic, and metabolomics landscapes. These technologies have helped decipher multiple molecular pathways dysregulated in breast cancer. First-generation 'omics analyses considered each of these dimensions individually, but it is becoming increasingly clear that more holistic, integrative approaches are required to fully understand complex biological systems. The 'omics represent an exciting era of discovery in breast cancer research, although important issues need to be addressed to realize the clinical utility of these data through precision cancer care. How can the data be applied to predict response to molecular-targeted therapies? When should treatment decisions be based on tumor genetics rather than histology? And with the sudden explosion of "big data" from large 'omics consortia and new precision clinical trials, how do we now negotiate evidence-based pathways to clinical translation through this apparent sea of opportunity? The aim of this review is to provide a broad overview of 'omics technologies used in breast cancer research today, the current state-of-play in terms of applying this new knowledge in the clinic, and the practical and ethical issues that will be central to the public discussion on the future of precision cancer care.
我们对乳腺癌自然史的理解是随着研究其基因组、转录组、蛋白质组和代谢组学特征的技术一同发展的。这些技术有助于解析乳腺癌中多个失调的分子途径。第一代“组学”分析分别考量了这些层面中的每一个,但越来越明显的是,需要采用更全面、综合的方法才能充分理解复杂的生物系统。“组学”代表了乳腺癌研究中一个令人兴奋的发现时代,不过,要通过精准癌症治疗实现这些数据的临床应用,还需要解决一些重要问题。这些数据如何应用于预测对分子靶向疗法的反应?治疗决策何时应基于肿瘤遗传学而非组织学?随着来自大型“组学”联盟和新型精准临床试验的“大数据”突然激增,我们现在如何在这片看似充满机遇的海洋中,商议出基于证据的临床转化路径?本综述的目的是对当今乳腺癌研究中使用的“组学”技术、在临床应用这一新知识方面的现状,以及对于精准癌症治疗未来的公众讨论至关重要的实际和伦理问题进行广泛概述。