Hampel Harald, Goetzl Edward J, Kapogiannis Dimitrios, Lista Simone, Vergallo Andrea
AXA Research Fund & Sorbonne University Chair, Paris, France.
Sorbonne University, GRC n° 21, Alzheimer Precision Medicine (APM), AP-HP, Pitié-Salpêtrière Hospital, Paris, France.
Front Pharmacol. 2019 Mar 29;10:310. doi: 10.3389/fphar.2019.00310. eCollection 2019.
Systems biology studies have demonstrated that different (epi)genetic and pathophysiological alterations may be mapped onto a single tumor's clinical phenotype thereby revealing commonalities shared by cancers with divergent phenotypes. The success of this approach in cancer based on analyses of traditional and emerging body fluid-based biomarkers has given rise to the concept of liquid biopsy enabling a non-invasive and widely accessible precision medicine approach and a significant paradigm shift in the management of cancer. Serial liquid biopsies offer clues about the evolution of cancer in individual patients across disease stages enabling the application of individualized genetically and biologically guided therapies. Moreover, liquid biopsy is contributing to the transformation of drug research and development strategies as well as supporting clinical practice allowing identification of subsets of patients who may enter pathway-based targeted therapies not dictated by clinical phenotypes alone. A similar liquid biopsy concept is emerging for Alzheimer's disease, in which blood-based biomarkers adaptable to each patient and stage of disease, may be used for positive and negative patient selection to facilitate establishment of high-value drug targets and counter-measures for drug resistance. Going beyond the "one marker, one drug" model, integrated applications of genomics, transcriptomics, proteomics, receptor expression and receptor cell biology and conformational status assessments during biomarker-drug co-development may lead to a new successful era for Alzheimer's disease therapeutics. We argue that the time is now for implementing a liquid biopsy-guided strategy for the development of drugs that precisely target Alzheimer's disease pathophysiology in individual patients.
系统生物学研究表明，不同的（表观）遗传和病理生理改变可能映射到单个肿瘤的临床表型上，从而揭示具有不同表型的癌症之间的共性。基于对传统和新兴体液生物标志物的分析，这种方法在癌症研究中的成功催生了液体活检的概念，它能够提供一种非侵入性且广泛适用的精准医学方法，并在癌症管理方面带来了重大的范式转变。连续的液体活检为个体患者在疾病各个阶段的癌症演变提供了线索，从而能够应用个体化的基因和生物学指导疗法。此外，液体活检正在推动药物研发策略的转变，并支持临床实践，有助于识别可能进入基于通路的靶向治疗的患者亚组，而不仅仅由临床表型决定。类似的液体活检概念正在阿尔茨海默病领域出现，其中适用于每个患者和疾病阶段的血液生物标志物，可用于患者的阳性和阴性选择，以促进建立高价值的药物靶点和应对耐药性的措施。超越“一个标志物，一种药物”的模式，在生物标志物与药物共同开发过程中整合基因组学、转录组学、蛋白质组学、受体表达、受体细胞生物学和构象状态评估的应用，可能会为阿尔茨海默病治疗带来一个新的成功时代。我们认为，现在是时候实施一种液体活检指导的策略，来开发能够精确靶向个体患者阿尔茨海默病病理生理学的药物了。
