Biomarker-Drug and Liquid Biopsy Co-development for Disease Staging and Targeted Therapy: Cornerstones for Alzheimer’s Precision Medicine and Pharmacology

Frontiers in Pharmacology

Simone Lista¹  Edward J. Goetzl²  Harald Hampel⁴  Dimitrios Kapogiannis⁶  Andrea Vergallo⁶ 

[1] Sorbonne University Chair, Paris, France;Spine Institute (ICM), INSERM U 1127, CNRS UMR 7225, Boulevard de l’Hôpital, Paris, France;;AXA Research Fund &;Brain &Department of Medicine, University of California, San Francisco, San Francisco, CA, United States;Department of Neurology, Institute of Memory and Alzheimer’s Disease (IM2A), Pitié-Salpêtrière Hospital, AP-HP, Boulevard de l’Hôpital, Paris, France;Laboratory of Neurosciences, Intramural Research Program, National Institute on Aging, Baltimore, MD, United States;Sorbonne University, GRC n° 21, Alzheimer Precision Medicine (APM), AP-HP, Pitié-Salpêtrière Hospital, Paris, France;

关键词: Alzheimer’s disease;    liquid biopsy;    exosomes;    systems pharmacology;    precision medicine;   

DOI  :  10.3389/fphar.2019.00310

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown