Expert Review of Precision Medicine and Drug Development最新文献

{"title":"Global personalization of antibiotic therapy in critically ill patients","authors":"D. Lonsdale, J. Lipman","doi":"10.1080/23808993.2021.1874823","DOIUrl":"https://doi.org/10.1080/23808993.2021.1874823","url":null,"abstract":"ABSTRACT Introduction: Sepsis from bacterial infection remains a significant cause of morbidity and mortality. Antibiotic use continues to increase in the community and secondary care. This is driven by the potential benefits to the individual patient of a course of antibiotics. Far less attention is given to the potential adverse effects of antibiotic use in our view. These costs may be significant to both the individual and society. Areas covered: We review the evidence underpinning the costs and benefits of antibiotic use. We also discuss strategies to personalize medicine in this area that maximize the benefit to cost ratio for patients and society. Expert opinion: The body’s innate immune response to infection is similar to that of other inflammatory insults. Our view is as clinicians we need to differentiate these responses and hence require an accurate method to determine a diagnosis of a bacterial infection and monitor illness severity. Without this, clinicians will continue to prescribe significant volumes of unnecessary antibiotics in cases of non-bacterial inflammatory states.","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2021-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23808993.2021.1874823","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45396495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mutation-dependent treatment approaches for patients with complex multiple myeloma","authors":"F. Theodorakakou, M. Dimopoulos, E. Kastritis","doi":"10.1080/23808993.2021.1893605","DOIUrl":"https://doi.org/10.1080/23808993.2021.1893605","url":null,"abstract":"ABSTRACT Introduction: Multiple myeloma is a complex hematologic malignancy that is considered incurable. The increasing comprehension of the genomic complexity has provided new insights into the therapeutic landscape of the disease. Next-generation sequencing studies have identified numerous driver gene mutations and alterations in signaling pathways, implicated in pathobiology and disease progression. Areas covered: Molecular tailored therapies against specific genetic alterations are under development in preclinical studies. These alterations include mutations in BRAF/KRAS/NRAS, FGFR3, overexpression of BCL2, and abberation in pathways such as MYC, JAK/STAT, NFκB, and PI3K/AKT/mTOR. Some of these novel anti-myeloma agents have entered clinical setting, as well. The question of whether these agents should be given as monotherapy or in combination with contemporary regimens is being addressed in ongoing trials. In the current review we present an up-to-date overview of targeted therapies MM. Expert opinion: Although fully personalized MM therapy is nowhere near, new technologies that allow rapid, detailed (and at a feasible cost) evaluation of the genetic content of myeloma on an individual basis may actually allow the development of therapies based on molecular profiling. These regimens may also have the potential to predict prognosis and achieve durable responses when established therapies are unable to overcome drug resistance.","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2021-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23808993.2021.1893605","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43391171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The combination of encorafenib and binimetinib for the treatment of patients with BRAF-mutated advanced, unresectable, or metastatic melanoma: an update","authors":"E. McClure, Ayushi S. Patel, Michael J. Carr, James X. Sun, J. Zager","doi":"10.1080/23808993.2021.1847639","DOIUrl":"https://doi.org/10.1080/23808993.2021.1847639","url":null,"abstract":"ABSTRACT Introduction: In the treatment of advanced BRAF-mutated melanoma, selective regulation of the MAPK pathway with BRAF and MEK inhibition has emerged as one of the mainstays of therapy. Areas covered: Introduction of MAPK pathway. Current data on BRAF inhibition from phase I, II, and III trials in the setting of unresectable disease. Current data on encorafenib and binietinib, their chemistry, pharmacokinetic, and pharmacodynamic properties. Discussion on use of encorafenib therapy as a single agent as well as in combination with binimetinib and other systemic therapies. Expert opinion: BRAF inhibition with encorafenib exhibits substantial antitumor activity with less paradoxical MAPK pathway activation leading to treatment resistance. Combination therapy with binimetinib improves response rate, progression-free survival, and overall survival in patients with BRAF-mutated unresectable, metastatic melanoma. Serious adverse events, including development of cutaneous malignancies, are reported at lower rates with combination therapy, while less severe events such as pyrexia can be more common.","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2021-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23808993.2021.1847639","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46573912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How feasible is the stratification of osteoarthritis phenotypes by means of artificial intelligence?","authors":"Amanda E Nelson","doi":"10.1080/23808993.2021.1848424","DOIUrl":"https://doi.org/10.1080/23808993.2021.1848424","url":null,"abstract":"Osteoarthritis (OA) is a common and serious disease that involves all of the tissues of an affected joint (e.g., cartilage, bone, meniscus, tendon/ligament, synovium) and can affect one or multiple joints in an individual person, most often the finger joints, knees, hips, and spine [1]. OA is a major and growing contributor to disability worldwide and is associated with increased comorbidity and excess mortality [1]. Management of OA is focused on modestly effective lifestyle/behavioral interventions such as increased physical activity and weight loss, with pharmacologic therapies directed toward temporary symptomatic relief [2]. Although many clinical trials have been conducted, there are still no effective disease-modifying therapies, no proven way to prevent progression, and no cure. This is at least in part due to the lack of appreciation of, and accounting for, the heterogeneity of this complex disease in trials to date [3]. In general, most trials have enrolled all individuals with knee OA defined as the presence of symptoms (e.g., pain, aching, and stiffness) and moderate to severe radiographic change (e.g., osteophytes or joint space narrowing) in at least one knee. This does not account for the diverse mechanisms of disease development, which can be due to mechanical dysfunction, prior injury, metabolic factors, inflammation, or combinations of these. Nor does it address the diversity of presentations, burden of disease (i.e., number/severity of involved joints), chronicity, or numerous other aspects of the disease process in a given individual that may subsequently affect their response to the proposed therapy. This brief editorial review seeks to summarize recent work in the area of machine learning and osteoarthritis phenotyping.","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23808993.2021.1848424","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25556237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Math, magnets, and medicine: enabling personalized oncology.","authors":"David A Hormuth, Angela M Jarrett, Guillermo Lorenzo, Ernesto A B F Lima, Chengyue Wu, Caroline Chung, Debra Patt, Thomas E Yankeelov","doi":"10.1080/23808993.2021.1878023","DOIUrl":"10.1080/23808993.2021.1878023","url":null,"abstract":"Oden Institute for Computational Engineering and Sciences, The University of Texas at Austin, Austin, TX, USA; Livestrong Cancer Institutes, The University of Texas at Austin, Austin, TX, USA; Department of Civil Engineering and Architecture, University of Pavia, Pavia, Italy; Texas Advanced Computing Center, The University of Texas at Austin, Austin, TX, USA; Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Texas Oncology, Austin, TX, USA; Departments of Biomedical Engineering, The University of Texas at Austin, Austin, TX, USA; Department of Diagnostic Medicine, The University of Texas at Austin, Austin, TX, USA; Department of Oncology, The University of Texas at Austin, Austin, TX, USA; Departments of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23808993.2021.1878023","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38941876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GUCY2C as a biomarker to target precision therapies for patients with colorectal cancer.","authors":"Amanda N Lisby,&nbsp;John C Flickinger,&nbsp;Babar Bashir,&nbsp;Megan Weindorfer,&nbsp;Sanjna Shelukar,&nbsp;Madison Crutcher,&nbsp;Adam E Snook,&nbsp;Scott A Waldman","doi":"10.1080/23808993.2021.1876518","DOIUrl":"https://doi.org/10.1080/23808993.2021.1876518","url":null,"abstract":"<p><strong>Introduction: </strong>Colorectal cancer (CRC) is one of the most-deadly malignancies worldwide. Current therapeutic regimens for CRC patients are relatively generic, based primarily on disease type and stage, with little variation. As the field of molecular oncology advances, so too must therapeutic management of CRC. Understanding molecular heterogeneity has led to a new-found promotion for precision therapy in CRC; underlining the diversity of molecularly targeted therapies based on individual tumor characteristics.</p><p><strong>Areas covered: </strong>We review current approaches for the treatment of CRC and discuss the potential of precision therapy in advanced CRC. We highlight the utility of the intestinal protein guanylyl cyclase C (GUCY2C), as a multi-purpose biomarker and unique therapeutic target in CRC. Here, we summarize current GUCY2C-targeted approaches for treatment of CRC.</p><p><strong>Expert opinion: </strong>The GUCY2C biomarker has multi-faceted utility in medicine. Developmental investment of GUCY2C as a diagnostic and therapeutic biomarker offers a variety of options taking the molecular characteristics of cancer into account. From GUCY2C-targeted therapies, namely cancer vaccines, CAR-T cells, and monoclonal antibodies, to GUCY2C agonists for chemoprevention in those who are at high risk for developing colorectal cancer, the utility of this protein provides many avenues for exploration with significance in the field of precision medicine.</p>","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23808993.2021.1876518","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38941879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical application of personalized rheumatoid arthritis risk information: Translational epidemiology leading to precision medicine.","authors":"Jeffrey A Sparks","doi":"10.1080/23808993.2021.1857237","DOIUrl":"https://doi.org/10.1080/23808993.2021.1857237","url":null,"abstract":"Over the last few decades, major progress has been made in identifying risk factors for the development of rheumatoid arthritis (RA), a relatively common chronic disease characterized by inflammatory arthritis with complex etiology [1]. These include both nonmodifiable factors, such as demographics and genetics [2], and potentially modifiable factors, such as cigarette smoking and elevated body mass index [3]. Clinicians may wonder how this growing knowledge may someday apply to clinical practice. A traditional view of epidemiology uses risk factors to passively elucidate an overall disease process or identify trends on a population level. In the context of precision medicine, epidemiologic findings may be used to deconstruct disease heterogeneity [4] while informing the development and implementation of personalized interventions [5], or ‘translational epidemiology.’ This article illustrates two recent translational epidemiologic studies in rheumatology that sought to incorporate personalized risk factors into a clinical framework leading us closer toward precision medicine. A number of important clinical risk tools, such as the Framingham Risk Score for cardiovascular disease [6], have been successfully implemented. While these tools have been validated, they may be inaccurate on an individual level [7] or in distinct populations [6] and may have no ability to incorporate novel risk factors or consider interactions between factors [8]. These tools were typically developed for clinicians to help risk-stratify, screen, treat, or prognosticate; they were less oriented toward assisting in diagnosis. While genetic factors are increasingly tested in clinical practice, interpretation is usually not easily integrated with other risk factors. The effects of traditional clinical risk tools on the patient’s willingness to accept interventions, optimizing health behaviors, and psychologic impact have not been the focus. Thus, traditional clinical risk tools are not directly transferable toward a precision medicine framework. A recent randomized controlled trial sought to investigate the effects of a personalized tool for chronic disease risk over one year on motivation to improve health behaviors, knowledge of risk factors, and psychologic impact. The Personalized Risk Estimator for RA (PRE-RA) Family Study developed a comprehensive RA risk tool [9] that personalized RA risk to demographics, family history, genetics (HLA-DRB1 ‘shared epitope,’ the major genetic RA risk factor [10]), biomarkers (two RA-related serum autoantibodies), and four modifiable RA-related risk behaviors (cigarette smoking, sedentary physical activity, low fish intake, and poor dental hygiene) [11]. The web-based PRE-RA risk tool provided personalized results about overall RA risk (using both relative and absolute risk scales) and the components/explanation of risk [11]. The PRERA Family Study randomized 238 unaffected first-degree relatives of RA patients to receive the personalized","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23808993.2021.1857237","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39011744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Use of Blood Biomarkers in Precision Medicine for the Primary Prevention of Atherosclerotic Cardiovascular Disease: a Review.","authors":"Ty Sweeney,&nbsp;Renato Quispe,&nbsp;Thomas Das,&nbsp;Stephen P Juraschek,&nbsp;Seth S Martin,&nbsp;Erin D Michos","doi":"10.1080/23808993.2021.1930531","DOIUrl":"https://doi.org/10.1080/23808993.2021.1930531","url":null,"abstract":"<p><strong>Introduction: </strong>A biomarker is a substance, structure, or process that indicates the presence of a disease, infection, or environmental exposure. Clinically useful biomarkers are measurable, improve diagnostic or prognostic performance, and ultimately aid clinicians in determining the initiation, duration, or magnitude of therapy.</p><p><strong>Areas covered: </strong>The purpose of this review is to explore the roles of various blood biomarkers of atherosclerotic cardiovascular disease (ASCVD) and how their use may improve the precision with which clinicians can identify, treat, and ultimately prevent ASCVD. Our review will include lipid biomarkers, markers of cardiac injury and wall stress, markers of inflammation, and a few others.</p><p><strong>Expert opinion: </strong>Several biomarkers have recently been highlighted as \"risk-enhancing factors\" in the 2019 American College of Cardiology/American Heart Association Guideline for the Primary Prevention of ASCVD, which can help guide shared decision-making. These included elevated low-density lipoprotein cholesterol, triglycerides, lipoprotein(a), apolipoprotein B, or high-sensitivity C-reactive protein. However, some other biomarkers mentioned in this review are not commonly used despite showing initial promise as prognostic of ASCVD risk, as it is not clear how treatment decisions should be changed after their measurement among asymptomatic individuals. Future studies should focus on whether biomarker-directed management strategies can improve clinical outcomes.</p>","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23808993.2021.1930531","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39348990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The evolution of patient-specific precision biomarkers to guide personalized heart-transplant care.","authors":"Mario C Deng","doi":"10.1080/23808993.2021.1840273","DOIUrl":"https://doi.org/10.1080/23808993.2021.1840273","url":null,"abstract":"<p><strong>Introduction: </strong>In parallel to the clinical maturation of heart transplantation over the last 50 years, rejection testing has been revolutionized within the systems biology paradigm triggered by the Human Genome Project.</p><p><strong>Areas covered: </strong>We have co-developed the first FDA-cleared diagnostic and prognostic leukocyte gene expression profiling biomarker test in transplantation medicine that gained international evidence-based medicine guideline acceptance to rule out moderate/severe acute cellular cardiac allograft rejection without invasive endomyocardial biopsies. This work prompted molecular re-classification of intragraft biology, culminating in the identification of a pattern of intragraft myocyte injury, in addition to acute cellular rejection and antibody-mediated rejection. This insight stimulated research into non-invasive detection of myocardial allograft injury. The addition of a donor-organ specific myocardial injury marker based on donor-derived cell-free DNA further strengthens the non-invasive monitoring concept, combining the clinical use of two complementary non-invasive blood-based measures, host immune activity-related risk of acute rejection as well as cardiac allograft injury.</p><p><strong>Expert opinion: </strong>This novel complementary non-invasive heart transplant monitoring strategy based on leukocyte gene expression profiling and donor-derived cell-free DNA that incorporates longitudinal variability measures provides an exciting novel algorithm of heart transplant allograft monitoring. This algorithm's clinical utility will need to be tested in an appropriately designed randomized clinical trial which is in preparation.</p>","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23808993.2021.1840273","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25528263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteome-based pathology: the next frontier in precision medicine.","authors":"Michael H Roehrl,&nbsp;Victor B Roehrl,&nbsp;Julia Y Wang","doi":"10.1080/23808993.2021.1854611","DOIUrl":"https://doi.org/10.1080/23808993.2021.1854611","url":null,"abstract":"Proteins are the true machines of life. Protein enzymes carry out virtually all complex chemical transformations in living organisms, such as nucleic acid synthesis and replication, posttranslational modifications, carbohydrate and lipid metabolism, hormone biosynthesis, proteolysis, and many more. Proteins provide functional context to cells, tissues, and organisms in the form of receptors, signaling cascades, channels, and transporters. Proteins are also major structural components of the cytoskeleton and extracellular matrices. The pathobiology of virtually all diseases can be understood as the malfunctioning of any one or more of this myriad of actions that proteins perform in a spatially and temporally highly orchestrated manner. By contrast, many diseases, especially cancers, continue to be viewed in a nucleic acid-based genomic and mutation-centric manner, but is this good enough?","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23808993.2021.1854611","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25531384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}