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提供精准医疗的复杂性:机遇与挑战。

Complexity of Delivering Precision Medicine: Opportunities and Challenges.

作者信息

Davis Andrew A, McKee Amy E, Kibbe Warren A, Villaflor Victoria M

机构信息

From the Department of Medicine, Division of Hematology and Oncology, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL; Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD; Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC.

出版信息

Am Soc Clin Oncol Educ Book. 2018 May 23;38:998-1007. doi: 10.1200/EDBK_200279.

Abstract

Precision medicine has emerged as a tool to match patients with the appropriate treatment based on the precise molecular features of an individual patient's tumor. Although examples of targeted therapies exist resulting in dramatic improvements in patient outcomes, comprehensive genomic profiling of tumors has also demonstrated the incredible complexity of molecular alterations in tissue and blood. These sequencing methods provide opportunities to study the landscape of tumors at baseline and serially in response to treatment. These tools also serve as important biomarkers to detect resistance to treatment and determine higher likelihood of responding to particular treatments, such as immune checkpoint blockade. Federally funded and publicly available data repositories have emerged as mechanisms for data sharing. In addition, novel clinical trials are emerging to develop new ways of incorporating molecular matched therapy into clinical trials. Various challenges to delivery of precision oncology include understanding the complexity of advanced tumors based on evolving "omics" and treatment resistance. For physicians, determining when and how to incorporate genetic and molecular tools into clinic in a cost-effective manner is critical. Finally, we discuss the importance of well-designed prospective clinical trials, biomarkers such as liquid biopsies, the use of multidisciplinary tumor boards, and data sharing as evidence-based medicine tools to optimally study and deliver precision oncology to our patients.

摘要

精准医学已成为一种工具,可根据个体患者肿瘤的精确分子特征为患者匹配适当的治疗方法。尽管存在靶向治疗的例子,使患者的治疗效果有了显著改善,但肿瘤的全面基因组分析也显示出组织和血液中分子改变的惊人复杂性。这些测序方法为在基线时以及在治疗过程中连续研究肿瘤格局提供了机会。这些工具还可作为重要的生物标志物,用于检测对治疗的耐药性,并确定对特定治疗(如免疫检查点阻断)产生反应的更高可能性。联邦资助且公开可用的数据存储库已成为数据共享的机制。此外,新的临床试验正在涌现,以开发将分子匹配疗法纳入临床试验的新方法。精准肿瘤学的实施面临各种挑战,包括基于不断发展的“组学”和治疗耐药性来理解晚期肿瘤的复杂性。对医生而言,以具有成本效益的方式确定何时以及如何将基因和分子工具纳入临床至关重要。最后,我们讨论精心设计的前瞻性临床试验、液体活检等生物标志物、多学科肿瘤委员会的使用以及数据共享作为循证医学工具的重要性,以便最佳地研究精准肿瘤学并为患者提供治疗。

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