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      Precision Medicine: Steps along the Road to Combat Human Cancer

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          Abstract

          The diagnosis and treatment of diseases such as cancer is becoming more accurate and specialized with the advent of precision medicine techniques, research and treatments. Reaching down to the cellular and even sub-cellular level, diagnostic tests can pinpoint specific, individual information from each patient, and guide providers to a more accurate plan of treatment. With this advanced knowledge, researchers and providers can better gauge the effectiveness of drugs, radiation, and other therapies, which is bound to lead to a more accurate, if not more positive, prognosis. As precision medicine becomes more established, new techniques, equipment, materials and testing methods will be required. Herein, we will examine the recent innovations in assays, devices and software, along with next generation sequencing in genomics diagnostics which are in use or are being developed for personalized medicine. So as to avoid duplication and produce the fullest possible benefit, all involved must be strongly encouraged to collaborate, across national borders, public and private sectors, science, medicine and academia alike. In this paper we will offer recommendations for tools, research and development, along with ideas for implementation. We plan to begin with discussion of the lessons learned to date, and the current research on pharmacogenomics. Given the steady stream of advances in imaging mass spectrometry and nanoLC-MS/MS, and use of genomic, proteomic and metabolomics biomarkers to distinguish healthy tissue from diseased cells, there is great potential to utilize pharmacogenomics to tailor a drug or drugs to a particular cohort of patients. Such efforts very well may bring increased hope for small groups of non-responders and those who have demonstrated adverse reactions to current treatments.

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          MS-DIAL: Data Independent MS/MS Deconvolution for Comprehensive Metabolome Analysis

          Data-independent acquisition (DIA) in liquid chromatography tandem mass spectrometry (LC-MS/MS) provides more comprehensive untargeted acquisition of molecular data. Here we provide an open-source software pipeline, MS-DIAL, to demonstrate how DIA improves simultaneous identification and quantification of small molecules by mass spectral deconvolution. For reversed phase LC-MS/MS, our program with an enriched LipidBlast library identified total 1,023 lipid compounds from nine algal strains to highlight their chemotaxonomic relationships.
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            Personalized In Vitro and In Vivo Cancer Models to Guide Precision Medicine.

            Precision medicine is an approach that takes into account the influence of individuals' genes, environment, and lifestyle exposures to tailor interventions. Here, we describe the development of a robust precision cancer care platform that integrates whole-exome sequencing with a living biobank that enables high-throughput drug screens on patient-derived tumor organoids. To date, 56 tumor-derived organoid cultures and 19 patient-derived xenograft (PDX) models have been established from the 769 patients enrolled in an Institutional Review Board-approved clinical trial. Because genomics alone was insufficient to identify therapeutic options for the majority of patients with advanced disease, we used high-throughput drug screening to discover effective treatment strategies. Analysis of tumor-derived cells from four cases, two uterine malignancies and two colon cancers, identified effective drugs and drug combinations that were subsequently validated using 3-D cultures and PDX models. This platform thereby promotes the discovery of novel therapeutic approaches that can be assessed in clinical trials and provides personalized therapeutic options for individual patients where standard clinical options have been exhausted.Significance: Integration of genomic data with drug screening from personalized in vitro and in vivo cancer models guides precision cancer care and fuels next-generation research. Cancer Discov; 7(5); 462-77. ©2017 AACR.See related commentary by Picco and Garnett, p. 456This article is highlighted in the In This Issue feature, p. 443.
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              A vision for the future of genomics research.

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                Author and article information

                Journal
                Cells
                Cells
                cells
                Cells
                MDPI
                2073-4409
                09 September 2020
                September 2020
                : 9
                : 9
                : 2056
                Affiliations
                [1 ]Department of Biology, Brandeis University, Waltham, MA 02453, USA
                [2 ]Department of Neurology, Yale School of Medicine, New Haven, CT 06511, USA; khadir.raddassi@ 123456yale.edu
                [3 ]Sciex, Redwood City, CA 94065, USA; Joseph.Doktorski@ 123456sciex.com
                [4 ]Department of Medicine, King Saud Bin-Abdulaziz University, King Abdulaziz Medical City-National Guard Health Affairs, Riyadh 11426, Saudi Arabia
                Author notes
                Author information
                https://orcid.org/0000-0002-2508-9852
                Article
                cells-09-02056
                10.3390/cells9092056
                7563722
                32916938
                06872f07-b16b-4781-a447-56111253dfb6
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 21 July 2020
                : 01 September 2020
                Categories
                Review

                precision medicine,genomic,proteomic,metabolomics,biomarkers,pharmaco-genomics,cancer

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