Precision oncology based on omics data: The NCT Heidelberg experience
Precision oncology based on omics data: The NCT Heidelberg experience
复制标题
DOI：
10.1002/ijc.30828
复制
发表时间：
2017-09-01
影响因子：
6.4
通讯作者：
Froehling, Stefan
中科院分区：
文献类型：
--
作者：
Horak, Peter;Klink, Barbara;Froehling, Stefan
精确肿瘤学意味着能够预测哪些患者可能对特定的癌症治疗产生反应，这些治疗基于越来越准确的高分辨率分子诊断以及对个体肿瘤的功能和机制的理解。虽然可以通过不同的手段实现患者的分子分层，但一种有前途的方法是肿瘤DNA和RNA的下一代测序，它可以揭示具有直接临床意义的基因组改变。此外，某些遗传改变在多个组织学实体中共享，这提出了肿瘤是否应该通过分子谱而不是起源组织来治疗的根本问题。我们在这里描述MASTER（肿瘤根除研究的分子辅助分层），这是一个临床适用的平台，用于对所有组织学类型的晚期癌症年轻成人和罕见肿瘤患者进行前瞻性、生物学驱动的分层。我们说明了如何选择和同意的患者，样本处理，全外显子组/基因组和RNA测序，生物信息学分析，严格验证潜在的可行性研究结果，以及数据评估的标准化工作流程，由一个专门的分子肿瘤委员会使患者分类到不同的干预篮子和制定循证临床管理的建议。接下来的关键步骤将是通过合作和伙伴关系增加可以提供全面分子分析的患者数量，探索其他技术可以帮助患者分层和个性化治疗的方法，刺激临床指导的探索性研究项目，逐步从逐案评估靶向干预的治疗活性转向基因组学的对照临床试验-指导治疗。
Precision oncology implies the ability to predict which patients will likely respond to specific cancer therapies based on increasingly accurate, high-resolution molecular diagnostics as well as the functional and mechanistic understanding of individual tumors. While molecular stratification of patients can be achieved through different means, a promising approach is next-generation sequencing of tumor DNA and RNA, which can reveal genomic alterations that have immediate clinical implications. Furthermore, certain genetic alterations are shared across multiple histologic entities, raising the fundamental question of whether tumors should be treated by molecular profile and not tissue of origin. We here describe MASTER (Molecularly Aided Stratification for Tumor Eradication Research), a clinically applicable platform for prospective, biology-driven stratification of younger adults with advanced-stage cancer across all histologies and patients with rare tumors. We illustrate how a standardized workflow for selection and consenting of patients, sample processing, whole-exome/genome and RNA sequencing, bioinformatic analysis, rigorous validation of potentially actionable findings, and data evaluation by a dedicated molecular tumor board enables categorization of patients into different intervention baskets and formulation of evidence-based recommendations for clinical management. Critical next steps will be to increase the number of patients that can be offered comprehensive molecular analysis through collaborations and partnering, to explore ways in which additional technologies can aid in patient stratification and individualization of treatment, to stimulate clinically guided exploratory research projects, and to gradually move away from assessing the therapeutic activity of targeted interventions on a case-by-case basis toward controlled clinical trials of genomics-guided treatments.