Expert Review of Precision Medicine and Drug Development最新文献

{"title":"An evaluation of selumetinib for the treatment of neurofibromatosis type 1-associated symptomatic, inoperable plexiform neurofibromas","authors":"L. Metrock, M. Lobbous, B. Korf","doi":"10.1080/23808993.2021.1917989","DOIUrl":"https://doi.org/10.1080/23808993.2021.1917989","url":null,"abstract":"ABSTRACT Introduction: Plexiform neurofibromas (PNs) are present in up to half of patients with neurofibromatosis type 1 (NF1). PNs consist of a proliferation of abnormal cells in the nerve sheath and can lead to significant comorbidities. Most PNs are diagnosed in early childhood when the most rapid growth rate generally occurs. Historically there has been a paucity of effective treatment options for patients with PNs, with surgery being the standard of care. As knowledge has increased regarding the NF1 gene and the function of its protein product neurofibromin, therapies targeting the Ras signaling pathway have been tested, first in preclinical models and subsequently in clinical trials. Areas covered: This review focuses on selumetinib (KOSELUGOTM; AZD6244, ARRY-142,886) and the management of PNs. A literature search was undertaken using PubMed with keywords ‘neurofibromatosis,’ ‘plexiform neurofibromas,’ ‘selumetinib,’ and ‘MEK inhibitor.’ Expert opinion: Selumetinib is the first FDA approved drug for the treatment of PNs. Prior to its development, options for patients with PNs causing morbidity were limited. Surgical intervention can be difficult, debilitating, and often futile. With the efficacy seen in the phase 1 and 2 trials for patients with NF1-associated PNs, the outlook has become one of the hope and excitement.","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":"6 1","pages":"239 - 246"},"PeriodicalIF":1.2,"publicationDate":"2021-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23808993.2021.1917989","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49165386","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":"Value of digital biomarkers in precision medicine: implications in cancer, autoimmune diseases, and COVID-19","authors":"E. Capobianco, Marcus John Beasley","doi":"10.1080/23808993.2021.1924055","DOIUrl":"https://doi.org/10.1080/23808993.2021.1924055","url":null,"abstract":"Based on the patient’s characteristics, precision medicine (PM) aims to optimize the time of administration of the most appropriate medicine with the minimum risk of toxicity. This is a multidimensional problem due to the varied disease course and therapeutic responses of patients. General factors, such as genetics, epigenetics, environment, ethnicity, adherence, lifestyle, and diet, determine these outcomes. In clinical trials, some drugs may be not beneficial or even harmful for a given ethnic or co-morbid group. Partial response is also observed outside trials, as the most commonly used drugs show high efficacy in relatively few patients. Therefore, what we call ‘imprecise medicine’ is the first challenge of PM due to the assumption underlying clinical practice that disease treatment and prevention strategies developed at the population level are expected to be accurate when applied at the individual level. The complexity that drives the variations in patient profiles depends on the heterogeneity of information obtained from large volumes of genetic, serological, biochemical, and diagnostic imaging data. These represent dimensions that need harmonization and integration with lifestyle and environmental factors. The second challenge is with assessing the benefits of the data dimensions, such as diagnostic improvements, earlier interventions, increased drug efficiency, and better-targeted treatments. To accommodate the heterogeneity of the etiologies, clinical symptoms, and treatment responses of patients in clinical practice, a revised clinical approach is recommended [1]. The first step is the development of a machine learning (ML)-assisted risk assessment model (see, for instance [2],) followed by the identification of the robust multimodal data-driven prognostic indicators (see, for instance [3],). These two efforts require new strategies for integrating heterogeneous information from different structured and unstructured data sources (electronic health records (EHRs), administrative databases, bioimaging archives, self-quantified measurements, etc.). Big Data has introduced a new paradigm for population-based studies that comes with challenges. For instance, the validity of such studies is based on the diagnostic accuracy used for all cases. A critical problem is the variability of the methods used to perform validations. Currently, there are challenges with validating most disease classification algorithms, and this complicates the assessment of their potential for population studies. Model validation facilitates safer interpretability of the correlations between diverse data types revealed by the models. Data-centric perspectives of complex diseases facilitate their definition as heterogeneous processes that have multifaceted causes, courses of evolution, treatments, and patient’s disease trajectories from the observed responses to treatment (see [4–6], among many other examples). These trajectories differ with each patient and, therefore","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":"6 1","pages":"235 - 238"},"PeriodicalIF":1.2,"publicationDate":"2021-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23808993.2021.1924055","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43378046","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 changing role of the pathologist in the era of targeted therapy in personalized medicine","authors":"G. D’Abbronzo, Renato Franco","doi":"10.1080/23808993.2021.1923400","DOIUrl":"https://doi.org/10.1080/23808993.2021.1923400","url":null,"abstract":"For a long time, the pathologist has mainly been dedicated to the morphological diagnosis, including macroscopic and microscopic examination of organs and tissues. Moreover, interaction between clinicians and pathologists was limited to the morphological diagnostic reports provided by pathologists. Recently, medical science has dramatically changed due to technological progress, recent discoveries in cellular and molecular pathways, the growing sub-specialization in the medical fields, the need to individualize oncological therapies. Indeed, due to the development of an increasingly individualbased therapy, the ‘companion diagnostic,’ specifically analyzing tumor markers able to predict the response of the patients to targeted therapies [1]. Thus, while the previous approach in diagnostic pathology were addressed to define prognostic biomarkers, currently the pathologists are required to identify biomarkers useful to predict patient’s potential response to target drugs [2]. For this reasons, classifications of the diseases, particularly neoplasms, enriched of immunohistochemical and molecular features. In this scenario, the pathologist has gone beyond the morphological diagnosis, definitively entering the patients’ clinical management, and leading the therapeutic addresses. Indeed, pathologists in a synergic collaboration with molecular biologists can provide necessary molecular information useful for a complete diagnosis. Therefore, pathologists become the final certifier of a complex diagnostic process, being medical professionals with the required skills to integrate morphological and molecular information in a report, including diagnosis and predictive biomarkers. This integrated information allows clinicians to choose the best therapeutic procedure for the individual patient (e.g. chemotherapy or immunotherapy or gene therapy) [3].","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":"6 1","pages":"295 - 297"},"PeriodicalIF":1.2,"publicationDate":"2021-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23808993.2021.1923400","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48823521","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":"Precision medicine for the treatment of triple negative breast cancer: opportunities and challenges","authors":"M. Sadiq, Juliette Servante, S. Madhusudan","doi":"10.1080/23808993.2021.1920834","DOIUrl":"https://doi.org/10.1080/23808993.2021.1920834","url":null,"abstract":"ABSTRACT Introduction: Triple negative breast cancer (TNBC) is a challenging disease generally following an aggressive clinical phenotype with poor survival outcomes. Scarcity of druggable targets coupled with molecular and genetic diversity has raised barriers in effective management of this disease; however, novel therapeutic strategies are on the horizon. Areas covered: We aim to present an overview of promising drugs that have emerged from preclinical studies undergoing investigation in early and late clinical trials alongside current challenges in the implementation of these in clinic. Expert opinion: The advent of immunotherapy and PARP inhibitors has finally started to diversify the cytotoxic chemotherapy-dependent treatment portfolio for TNBC. During this process, numerous challenges around novel biomarker discovery, optimum patient selection and combinatorial toxicity have been exposed. There is a clear need to further our understanding of the molecular pathways involved in the evolution of TNBC to optimize targets and explain inadequacies of current investigational treatments. We expect progressive expansion in diagnostic and prognostic biomarker panels allowing for further personalization of TNBC treatment.","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":"6 1","pages":"259 - 270"},"PeriodicalIF":1.2,"publicationDate":"2021-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23808993.2021.1920834","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42836353","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":"An update on immunotherapy in uro-oncology","authors":"A. Cimadamore, A. Rizzo, V. Mollica, F. Massari, A. López-Beltran, M. Scarpelli, Liang Cheng, M. Santoni, R. Montironi","doi":"10.1080/23808993.2021.1911638","DOIUrl":"https://doi.org/10.1080/23808993.2021.1911638","url":null,"abstract":"Section of Pathological Anatomy, Polytechnic University of the Marche Region, School of Medicine, United Hospitals, Ancona, Italy; Division of Oncology, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy; Department of Surgery, Cordoba University Medical School, Cordoba, Spain; Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, USA; Oncology department, Macerata Hospital, Macerata, Italy","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":"6 1","pages":"229 - 233"},"PeriodicalIF":1.2,"publicationDate":"2021-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23808993.2021.1911638","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45847278","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":"Considerations on the mechanics and sample sizes for early trials of targeted agents and immunotherapy in oncology","authors":"E. Coart, E. Saad","doi":"10.1080/23808993.2021.1915693","DOIUrl":"https://doi.org/10.1080/23808993.2021.1915693","url":null,"abstract":"ABSTRACT Introduction: Precision medicine is impacting clinical practice and drug development in oncology, promoting notable changes in the design of early-phase cancer trials. There is increasing pressure on sponsors and clinical trialists to strike the right balance between speed and reliability in the design and implementation of such trials, which now commonly assess activity in expansion cohorts. Areas covered: We discuss methodological issues related to trial design and sample sizes for phase 1 trials with expansion cohorts and phase 1/2 trials. We review the pertinent literature, present fictitious cases to illustrate the different designs, and discuss their advantages and disadvantages, with a focus on randomized designs in which an experimental and a control treatment are assessed. Expert Opinion: Designing a phase 1 trial with expansion cohorts requires statistical input and explicit consideration about interpretation of future results. There is currently insufficient emphasis on the role of randomization in expansion cohorts and phase 2 components of early-phase trials. The results from single-arm cohorts may be misleading due to selection bias, but comparative randomized trials may not be feasible in many cases due to budget constraints or ethical arguments. Randomized, non-comparative trials with a control arm used for calibration of historical results are an interesting intermediate solution between single-arm expansion cohorts and randomized comparative studies.","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":"6 1","pages":"271 - 280"},"PeriodicalIF":1.2,"publicationDate":"2021-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23808993.2021.1915693","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48850348","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":"Slotting metabolomics into routine precision medicine","authors":"M. Mussap, A. Noto, C. Piras, L. Atzori, V. Fanos","doi":"10.1080/23808993.2021.1911639","DOIUrl":"https://doi.org/10.1080/23808993.2021.1911639","url":null,"abstract":"ABSTRACT Introduction Despite an impressive amount of metabolomics studies in animal models and humans, most findings have not yet translated into the clinical setting, and the road ahead remains still long. Areas covered This review provides the most challenging applications of clinical metabolomics testing in human health and disease. Personalized clinical metabolomics testing is incorporated within the test panel to diagnose inborn errors of metabolism, optimize dietary regimens, and discover and develop new drugs. The potential routine utilization of metabolomics in precision medicine has been revised in cancer and nutrition. The association between metabolomics with artificial intelligence and machine learning may open emerging perspectives for more effective utilization and timely introduction of clinical metabolomics testing in the care of patients with acute and chronic diseases. Expert opinion In conclusion, slotting metabolomics into routine precision medicine implies the direct relationship between metabolomic results and clinical decision-making, similarly to any other clinical test result, as well as it requires the application of clinical laboratory standards, protocols, training, the oversight to a global biochemical profiling technology, and the availability of metabolic profiles from reference populations, defining cutoff values and decision levels.","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":"6 1","pages":"173 - 187"},"PeriodicalIF":1.2,"publicationDate":"2021-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23808993.2021.1911639","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42840621","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":"Ivosidenib in IDH-mutant cholangiocarcinoma: where do we stand?","authors":"A. Rizzo, A. Ricci, G. Brandi","doi":"10.1080/23808993.2021.1915126","DOIUrl":"https://doi.org/10.1080/23808993.2021.1915126","url":null,"abstract":"ABSTRACT Introduction: Cholangiocarcinomas (CCAs) are rare and heterogeneous malignancies associated with poor prognosis, with most of the patients presenting with advanced disease at diagnosis. The recent advent of molecular profiling has led to the identification of several druggable genetic aberrations, and among these, there is an increasing interest in isocitrate dehydrogenase-1 (IDH-1) mutations, with the IDH-1 inhibitor ivosidenib that has reported interesting results in advanced CCA patients. Areas covered: Herein, we will critically discuss the current state of the art of ivosidenib in IDH-mutant CCA, especially focusing on efficacy and safety results of recent trials assessing this IDH-1 inhibitor. Expert opinion: According to the results of phase I studies and the recently published ClarIDHy phase III trial, the IDH-1 inhibitor ivosidenib seems to be associated with a manageable safety profile and interesting antitumor efficacy. In particular, the ClarIDHy showed that ivosidenib treatment reported improved progression-free survival (PFS) compared to placebo in previously treated patients, with median PFS of 2.7 and 1.4 months, respectively. However, several questions remain unanswered and the effective impact of ivosidenib in IDH-mutant CCA remains open.","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":"6 1","pages":"217 - 224"},"PeriodicalIF":1.2,"publicationDate":"2021-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23808993.2021.1915126","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44246783","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":"Dacomitinib as first-line treatment for EGFR mutation-positive non-small cell lung cancer","authors":"T. Reungwetwattana, N. Rohatgi, T. Mok, K. Prabhash","doi":"10.1080/23808993.2021.1909420","DOIUrl":"https://doi.org/10.1080/23808993.2021.1909420","url":null,"abstract":"ABSTRACT Introduction: Dacomitinib is a second-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI). Recent results from ARCHER 1050, the first randomized, open-label, Phase 3 trial of a second-generation vs. a first-generation EGFR TKI, showed that dacomitinib improves progression-free survival and overall survival compared with gefitinib as a first-line treatment in patients with EGFR mutation-positive advanced non-small cell lung cancer (NSCLC). Areas covered: We review the efficacy and safety of dacomitinib as a first-line treatment of EGFR mutation-positive NSCLC, including the management of toxicity, and evaluate the activity of dacomitinib against brain metastases. Additionally, the optimal treatment sequence given EGFR TKI choice, resistance mechanisms, activity against rare mutations, and real-world dosing is discussed. Expert opinion: The introduction of EGFR TKIs has changed the treatment strategy for patients with EGFR mutation-positive NSCLC. The second- and third-generation EGFR TKIs are the result of research elucidating mechanisms of resistance to first-generation EGFR TKIs. There is now more than one treatment option for patients with EGFR mutation-positive advanced NSCLC that improves survival, highlighting the need to more clearly understand the use of the right drug for the right person at the right time and how the appropriate treatment sequence may provide optimal outcomes for these patients.","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":"6 1","pages":"161 - 171"},"PeriodicalIF":1.2,"publicationDate":"2021-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23808993.2021.1909420","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45533208","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":"Personalized patient care with aggressive hematological malignancies in non-responders to first-line treatment","authors":"K. Miura, N. Iriyama, Y. Hatta, M. Takei","doi":"10.1080/23808993.2021.1903314","DOIUrl":"https://doi.org/10.1080/23808993.2021.1903314","url":null,"abstract":"ABSTRACT Introduction Whereas most patients with aggressive hematological malignancies can achieve disease remission after receiving current standard first-line chemotherapies, the prognosis of those with primary refractory disease remains poor. Conventional salvage chemotherapies are usually unsuccessful, but significant advances have been achieved in precision medicine for these patients in recent years. Areas covered This article presents a comprehensive review of current personalized care for patients with primary refractory aggressive hematological malignancies, focusing on acute leukemias and aggressive non-Hodgkin lymphomas. Expert opinions Salvage treatment for refractory acute myeloid leukemia (AML) should be personalized by the FMS-like tyrosine kinase 3 (FLT3) mutation status. Additionally, treatment for isocitrate dehydrogenase 1 or 2 (IDH1/2)-mutated refractory AML can be specified. Inotuzumab ozogamicin and blinatumomab are essential drugs for refractory B-cell acute lymphoblastic leukemia. These antibodies can be selected based on the disease status, such as measurable residual disease. For refractory diffuse large B-cell lymphoma, treatment options are different according to the cell-of-origin. Finally, accurate pathological phenotyping is an essential first step to optimize refractory peripheral T-cell lymphoma treatment. Although novel personalized approaches have improved the clinical outcomes of these patients, consolidation with hematopoietic stem cell transplantation has a vital role in most cases.","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":"6 1","pages":"203 - 215"},"PeriodicalIF":1.2,"publicationDate":"2021-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23808993.2021.1903314","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42194701","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}