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Expert Review of Precision Medicine and Drug Development最新文献

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Noninvasive biomarkers to guide intervention: toward personalized patient management in prostate cancer 指导干预的无创生物标志物:前列腺癌症患者个性化管理
IF 1.2 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2020-08-03 DOI: 10.1080/23808993.2020.1804866
M. Frantzi, E. Gómez-Gómez, H. Mischak
ABSTRACT Introduction Prostate cancer (PCa) is one of the most frequently diagnosed malignancies worldwide and is associated with high mortality. Broad screening through prostate-specific antigen analysis, along with an aging and growing population has resulted in a vast increase in PCa incidence. As not all PCa forms are life threatening, personalized management is of paramount importance to preserve survival and quality of life for the diagnosed patients. Owing to the complexity of PCa, noninvasive biomarkers for diagnosis, stratification and monitoring, are essential to tailor intervention among patients with different disease manifestations. Areas covered In this article, we aim to provide a critical assessment of the reported noninvasive biomarkers for PCa and their applicability according to the targeted clinical context. For this purpose, a systematic review of the literature published within the last five years was performed, focusing on noninvasive biomarkers to guide initial and repeated biopsies, stratify for active surveillance, monitor biochemical recurrence and metastasis, and adjust treatment for metastatic castration resistant PCa. Expert’s opinion Evidence from clinical trials on novel drugs and latest technological advancements, indicate several clinical applications for biomarkers to tailor intervention throughout PCa progression, toward a more personalized medicine approach in PCa clinical management.
摘要简介癌症是全球最常见的恶性肿瘤之一,与高死亡率相关。通过前列腺特异性抗原分析进行的广泛筛查,以及人口的老龄化和增长,导致前列腺癌发病率大幅增加。由于并非所有PCa形式都有生命危险,因此个性化管理对于保持确诊患者的生存率和生活质量至关重要。由于前列腺癌的复杂性,用于诊断、分层和监测的非侵入性生物标志物对于针对不同疾病表现的患者进行干预至关重要。涵盖的领域在本文中,我们旨在根据目标临床背景,对所报道的PCa的非侵入性生物标志物及其适用性进行关键评估。为此,对过去五年内发表的文献进行了系统综述,重点关注非侵入性生物标志物,以指导初次和重复活检,对主动监测进行分层,监测生化复发和转移,并调整转移性去势耐药前列腺癌的治疗。专家意见来自新药临床试验和最新技术进步的证据表明,生物标志物在PCa进展过程中的几种临床应用,旨在为PCa临床管理提供更个性化的药物方法。
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引用次数: 4
A wide perspective of targeted therapies for precision medicine in autoimmune diseases 精准医学靶向治疗自身免疫性疾病的广阔前景
IF 1.2 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2020-07-31 DOI: 10.1080/23808993.2020.1804867
I. Miyagawa, S. Kubo, Yoshiya Tanaka
ABSTRACT Introduction The strategy of precision medicine is achieved by the stratification of patients and targeted therapy. It has been shown that the pathological conditions of patients who are classified or diagnosed with a single disease are actually diverse in almost all autoimmune diseases. Therefore, the practice of precision medicine is important for the treatment of patients with autoimmune diseases. Areas covered At present, precision medicine has not been achieved in any autoimmune disease. This article reviewed the attempted use of precision medicine for the treatment of systemic lupus erythematosus and psoriatic arthritis. Expert opinion Although multiple molecular-targeted therapies are available for the treatment of rheumatoid arthritis, the response to each treatment strategy often differs markedly among patients, and it is unclear how they are differentially selected for each patient. The establishment of precision medicine is especially important in heterogenous autoimmune diseases (e.g., systemic lupus erythematosus, psoriatic arthritis). Various symptoms must be improved at the same time, but the treatment options are limited. Therefore, the selection of the optimal treatment for individual patients is complex. Although some predictors of the treatment response are reported, precision medicine has not been sufficiently well evaluated in real clinical practice, especially for autoimmune diseases.
摘要引言精准医学的策略是通过对患者进行分层和靶向治疗来实现的。研究表明,在几乎所有的自身免疫性疾病中,被归类或诊断为单一疾病的患者的病理状况实际上是多样的。因此,精准医学的实践对自身免疫性疾病患者的治疗具有重要意义。所涵盖的领域目前,尚未在任何自身免疫性疾病中实现精准医学。本文综述了精准药物治疗系统性红斑狼疮和银屑病关节炎的尝试。专家意见尽管多种分子靶向疗法可用于治疗类风湿性关节炎,但患者对每种治疗策略的反应往往明显不同,目前尚不清楚如何对每种患者进行差异选择。精准医学的建立在异质性自身免疫性疾病(如系统性红斑狼疮、银屑病关节炎)中尤为重要。各种症状必须同时得到改善,但治疗选择有限。因此,为个别患者选择最佳治疗是复杂的。尽管已经报道了一些治疗反应的预测因素,但精准医学在实际临床实践中并没有得到足够好的评估,尤其是对于自身免疫性疾病。
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引用次数: 3
Ivosidenib for the treatment of relapsed or refractory acute myeloid leukemia with an IDH1 mutation Ivosidenib治疗IDH1突变的复发或难治性急性髓系白血病
IF 1.2 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2020-07-28 DOI: 10.1080/23808993.2020.1792286
F. Pasquier, C. Chahine, C. Marzac, S. de Botton
ABSTRACT Introduction Management of acute myeloid leukemia (AML) remains challenging, especially for relapsed or refractory (R/R) AML patients who display poor prognosis with conventional therapies. This underlined the need for new treatments in this population. Areas covered This review will focus on ivosidenib, an oral inhibitor of mutated isocitrate dehydrogenase 1 (IDH1) enzyme. Mechanisms of IDH1 mutations and their inhibition by ivosidenib will be cover, as well as clinical efficacy and safety of ivosidenib in R/R AML. Ivosidenib has been approved by the FDA for R/R AML patients with IDH1 mutation in July 2018 and for unfit AML patients with IDH1 mutation as first line treatment in May 2019. Expert commentary Ivosidenib induces impressive response rates in R/R AML, a population of bad prognosis. Nevertheless, primary and acquired resistances to ivosidenib have been recently described, underlining importance of the ongoing clinical trials with ivosidenib in combination with standard chemotherapy, hypomethylating agents or other targeted therapies.
摘要简介急性髓细胞白血病(AML)的治疗仍然具有挑战性,尤其是对于那些用传统疗法预后不佳的复发或难治性(R/R)AML患者。这突出了在这一人群中需要新的治疗方法。涵盖的领域本综述将重点介绍伊沃西替尼,一种突变异柠檬酸脱氢酶1(IDH1)酶的口服抑制剂。IDH1突变的机制及其对伊沃西替尼的抑制作用,以及伊沃西替尼在R/R AML中的临床疗效和安全性。Ivosidenib已于2018年7月被美国食品药品监督管理局批准用于IDH1突变的R/R AML患者,并于2019年5月被批准用于IDH1-突变的不适合AML患者的一线治疗。专家评论Ivosidenib在预后不良的R/R AML人群中诱导了令人印象深刻的应答率。尽管如此,最近已经描述了对伊沃西替尼的原发性和获得性耐药性,强调了正在进行的伊沃西替与标准化疗、低甲基化药物或其他靶向治疗相结合的临床试验的重要性。
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引用次数: 3
Deep sequencing as an approach to understanding the complexity and improving the treatment of multiple myeloma 深度测序作为了解复杂性和改善多发性骨髓瘤治疗的一种方法
IF 1.2 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2020-07-16 DOI: 10.1080/23808993.2020.1792285
Louis Williams, J. Caro, B. Razzo, E. Boyle, G. Morgan
ABSTRACT Introduction Multiple myeloma (MM) is plasma cell dyscrasia with marked variability in its clinical presentation and outcome, both of which are dictated by its underlying genetics. Next-generation sequencing techniques (NGS) have become essential to understanding the genomics of multiple myeloma. The exploitation of these advances in the clinic will require new clinical trial designs with endpoints that facilitate rapid readouts of success or failure and capture the impact of rare mutational events on outcomes. An understanding of NGS and its applications in multiple myeloma is therefore significant for both researchers and clinicians alike. Areas covered In this review, we summarize the significant advances that NGS has yielded in our understanding of the prognosis, clonal evolution, treatment and response assessment of multiple myeloma and its precursor conditions. We synthesize the relevant literature related to both genomics and the clinical management of MM, with articles selected based on our experience in the field. Expert opinion In the opinion of these authors, NGS will play a significant role in the future of precision medicine in multiple myeloma, especially as disease-specific panels and response adapted approaches to therapy gain traction. In the process, challenges related to cost, quality control, and standardization will need to be overcome.
摘要简介多发性骨髓瘤(MM)是一种浆细胞异常,其临床表现和转归具有显著的变异性,这两者都由其潜在的遗传学决定。下一代测序技术(NGS)已成为了解多发性骨髓瘤基因组学的关键。在临床上利用这些进展将需要新的临床试验设计,其终点有助于快速读出成功或失败,并捕捉罕见突变事件对结果的影响。因此,了解NGS及其在多发性骨髓瘤中的应用对研究人员和临床医生都具有重要意义。在这篇综述中,我们总结了NGS在理解多发性骨髓瘤及其前体条件的预后、克隆进化、治疗和反应评估方面取得的重大进展。我们综合了与MM的基因组学和临床管理相关的文献,并根据我们在该领域的经验选择了文章。专家意见在这些作者看来,NGS将在多发性骨髓瘤精准医学的未来发挥重要作用,特别是随着疾病特异性小组和适应反应的治疗方法的发展。在此过程中,需要克服与成本、质量控制和标准化相关的挑战。
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引用次数: 0
The pharmacogenetics of tacrolimus and its implications for personalized therapy in kidney transplant recipients 他克莫司的药物遗传学及其对肾移植受者个体化治疗的意义
IF 1.2 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2020-06-19 DOI: 10.1080/23808993.2020.1776107
M. Francke, B. D. de Winter, L. Elens, N. Lloberas, D. Hesselink
Twenty-five years after its approval by the FDA and EMA, tacrolimus remains the cornerstone of immunosuppressive treatment following solid organ transplantation [1,2]. The drug is highly effective ...
在获得美国食品药品监督管理局和欧洲药品管理局批准25年后,他克莫司仍然是实体器官移植后免疫抑制治疗的基石[1,2]。这种药非常有效。。。
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引用次数: 4
Treating central nervous system lymphoma in the era of precision medicine 精准医学时代治疗中枢神经系统淋巴瘤
IF 1.2 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2020-06-16 DOI: 10.1080/23808993.2020.1777853
Y. Garcilazo-Reyes, M. Ibañez-Juliá, I. Hernández-Verdin, L. Nguyen-Them, N. Younan, C. Houillier, K. Hoang-Xuan, A. Alentorn
ABSTRACT Introduction Primary central nervous system lymphoma (PCNSL) is a rare extra-nodal non-Hodgkin lymphoma that in the vast majority of cases belongs to diffuse large B-cell lymphoma (DLBCL) histology. The standard first-line treatment is based on high-dose methotrexate (HD-MTX) regimens. However, the majority of patients will relapse, leading to a poor prognosis of the disease. Areas covered Reviewed are the potential new therapeutic approaches in PCNSL. With the advent of tailored treatment, immunomodulators and immunotherapies are appearing as new promising therapeutic approaches for this orphan disease. This review seeks to summarize the novel approaches currently under evaluation. Expert opinion The therapeutic management of PCNSL is rapidly evolving with the description of PCNSL molecular alterations. However, due to the rarity of this disease, phase III clinical trials using new therapeutic drugs are still lacking. In addition, the vast majority of newly diagnosed PCNSL affect elderly patients, and specific and adapted clinical trials for this fragile population are warranted. Currently, the use of targeted therapies or immune-mediated treatments is only studied in relapsed/refractory (R/R) PCNSL, but the use of these approaches as a first-line treatment (compared with HD-MTX) could also be used as new promising approaches to decrease the toxicity associated with MTX regimens.
原发性中枢神经系统淋巴瘤(PCNSL)是一种罕见的淋巴结外非霍奇金淋巴瘤,绝大多数病例属于弥漫性大b细胞淋巴瘤(DLBCL)。标准的一线治疗是基于高剂量甲氨蝶呤(HD-MTX)方案。然而,大多数患者会复发,导致疾病预后不良。所涵盖的领域综述了PCNSL潜在的新治疗方法。随着量身定制治疗的出现,免疫调节剂和免疫疗法正成为治疗这种孤儿疾病的新方法。本综述旨在总结目前正在评估的新方法。专家意见随着PCNSL分子改变的描述,PCNSL的治疗管理正在迅速发展。然而,由于这种疾病的罕见性,使用新的治疗药物的III期临床试验仍然缺乏。此外,绝大多数新诊断的PCNSL影响的是老年患者,针对这一脆弱人群的特异性和适应性临床试验是有必要的。目前,靶向治疗或免疫介导治疗仅在复发/难治性(R/R) PCNSL中进行了研究,但将这些方法作为一线治疗(与HD-MTX相比)也可以作为新的有希望的方法来降低MTX方案相关的毒性。
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引用次数: 1
The outlook for precision medicine for the treatment of chronic hepatitis C infection: challenges and opportunities 精准医学治疗慢性丙型肝炎感染的前景:挑战与机遇
IF 1.2 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2020-06-09 DOI: 10.1080/23808993.2020.1764346
M. Frías, A. Rivero-Juarez, I. Machuca, Á. Camacho, A. Rivero
ABSTRACT Introduction This review focuses on the milestones and challenges of precision medicine in the natural history of HCV infection. Areas covered The manuscript summarizes the genetic and viral factors identified as predictive of outcome in HCV patients and discusses opportunities for a precision medicine approach to the management of patients with HCV infection. Special emphasis will be placed on the factors associated with response to treatment as well as other factors that can help the clinician in the management of patients after sustained virological response. Expert opinion The establishment of DAAs in recent years has led to a paradigmatic change in the natural history of hepatitis C virus infection. However, there are still challenges that precision medicine must solve, especially in the management of patients at high risk of liver complications after sustained virological response.
本文综述了HCV感染自然史中精准医学的里程碑和挑战。该手稿总结了被确定为HCV患者预后预测的遗传和病毒因素,并讨论了采用精准医学方法管理HCV感染患者的机会。将特别强调与治疗反应相关的因素,以及可以帮助临床医生在持续病毒学反应后管理患者的其他因素。专家意见近年来DAAs的建立导致了丙型肝炎病毒感染自然史的典型变化。然而,精准医学仍然面临着必须解决的挑战,特别是在持续病毒学反应后肝脏并发症高风险患者的管理方面。
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引用次数: 0
Phenotyping severe asthma: a rationale for biologic therapy 表型严重哮喘:生物治疗的基本原理
IF 1.2 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2020-06-07 DOI: 10.1080/23808993.2020.1776106
A. Vatrella, A. Maglio, S. Pellegrino, C. Pelaia, C. Stellato, G. Pelaia, C. Vitale
ABSTRACT Introduction Asthma is a complex disease with heterogeneity in etiology, triggers, clinical characteristics and different responses to pharmacological therapies. Areas covered Patients with severe uncontrolled asthma constitute a relatively small percentage, ranging from 5 to 10% of all asthmatics. These patients can benefit from targeted biological therapies developed in recent years. In fact, a better understanding of the etiopathological mechanisms of different phenotypes and endotypes of severe asthma have led to the availability of innovative biological therapies, able to modify the natural history of the disease by targeting molecules involved in airway inflammation. Several phenotypes based on clinical and physiologic variables and on inflammatory markers have been reported. Expert opinion The priority is to define the molecular process underlying the disease. In this context the recognition of T2 and non T2 inflammatory pathways, so called molecular phenotypes, represents the most reliable approach to drive the use of novel biological therapies. For this purpose, several biomarkers have been validated for identifying severe asthma phenotypes and for guiding the choice of the most appropriate treatment. The purpose of this review is to discuss the current knowledge about the molecular phenotypes of severe asthma, as well as the rationale underlying the use of existing biological drugs.
哮喘是一种复杂的疾病,在病因、触发因素、临床特征和对药物治疗的不同反应方面具有异质性。严重不受控制的哮喘患者占相对较小的百分比,占所有哮喘患者的5%至10%。这些患者可以从近年来发展的靶向生物疗法中获益。事实上,更好地了解不同表型和内源性哮喘的病因病理机制已经导致了创新生物疗法的可用性,能够通过靶向气道炎症相关分子来改变疾病的自然史。基于临床和生理变量和炎症标志物的几种表型已被报道。专家意见首先要确定这种疾病背后的分子过程。在这种情况下,对T2和非T2炎症途径的识别,即所谓的分子表型,代表了驱动新型生物疗法使用的最可靠方法。为此,已经验证了几种生物标志物用于识别严重哮喘表型并指导选择最合适的治疗方法。本综述的目的是讨论目前关于严重哮喘分子表型的知识,以及现有生物药物使用的基本原理。
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引用次数: 5
The emerging role of precision medicine in the treatment of ovarian cancer 精准医疗在癌症治疗中的新作用
IF 1.2 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2020-06-05 DOI: 10.1080/23808993.2020.1777854
G. Santangelo, G. Caruso, I. Palaia, F. Tomao, G. Perniola, V. Di Donato, M. Fischetti, L. Muzii, P. Benedetti Panici
ABSTRACT Introduction Ovarian cancer is the primary cause of gynecologic cancer death in women worldwide and it is generally diagnosed at an advanced stage. Although the current standard treatment based on extensive cytoreductive surgery and systemic chemotherapy results in a high complete remission rate, recurrences are extremely frequent and exhibit progressive chemotherapy resistance, thus posing a difficult clinical challenge. Areas covered In the era of precision medicine, the increasing knowledge of cancer genomics, proteomics, and immune milieu facilitated the development of new targeted therapies (e.g. antiangiogenic drugs, PARP inhibitors, immunotherapy, folate receptor inhibitors, growth factor signaling inhibitors), that could improve ovarian cancer paradigm of care. Expert opinion In this review article, we discuss recent advances in the management of ovarian cancer, highlighting the need for a modern, personalized, and multi-disciplinary approach and for new predictive biological markers that will allow to choose the best therapeutic option between chemotherapy, molecular targeted agents, and immunotherapy for each patient. In the future, modern combinations of targeted therapies will open new chances for ovarian cancer patients. The main goal is to turn an aggressive disease eventually into a manageable chronic condition.
摘要简介癌症是全球女性癌症死亡的主要原因,通常诊断为晚期。尽管目前基于广泛的细胞减灭术和全身化疗的标准治疗导致了高的完全缓解率,但复发极为频繁,并表现出进行性化疗耐药性,因此构成了困难的临床挑战。所涵盖的领域在精准医疗时代,癌症基因组学、蛋白质组学和免疫环境的知识不断增加,促进了新靶向治疗的发展(如抗血管生成药物、PARP抑制剂、免疫疗法、叶酸受体抑制剂、生长因子信号抑制剂),这可能会改善卵巢癌症的治疗模式。专家意见在这篇综述文章中,我们讨论了卵巢癌症治疗的最新进展,强调了对现代、个性化和多学科方法的需求,以及对新的预测性生物标志物的需求,这将使我们能够在化疗、分子靶向药物和免疫疗法之间为每位患者选择最佳治疗方案。未来,靶向治疗的现代组合将为卵巢癌症患者打开新的机会。主要目标是将一种侵袭性疾病最终转变为可控制的慢性疾病。
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引用次数: 3
Prognostic models to help predict patient responses to intravesical immunotherapy 预测患者膀胱内免疫治疗反应的预后模型
IF 1.2 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2020-06-01 DOI: 10.1080/23808993.2020.1768845
E. Laukhtina, D. D’andrea, B. Pradère, D. Enikeev, M. Abufaraj, S. Shariat
ABSTRACT Introduction Approximately 30–60% of patients treated with Bacillus Calmette-Guérin (BCG) for non-muscle invasive bladder cancer (NMIBC) eventually experience disease recurrence within 2 years. Parsimonious use of BCG and accurate identification of those patients who might benefit from this therapy is of paramount importance in order to avoid BCG wastage, improve patient counseling regarding alternative therapy, patient’s survival and quality of life. We summarized the current literature on predictive and prognostic models on intravesical BCG therapy for NMIBC. Areas covered Clinicopathologic features are the strongest predictors of BCG response. In addition, several tissue, serum and urinary biomarkers have been investigated. However, they have not been shown to be robust enough to be implemented in daily clinical routine. Therefore, genetic and epigenetic markers and features of the tumor microenvironment have been investigated. The relationship between Th1 and Th2 microenvironments, as well as its related serum and urine biomarkers, was shown to play an important role in prediction of response to BCG treatment. Expert opinion No single tumor biomarker has been shown to be robust enough to change clinical decision making. Discoveries in the genetic signature profile of bladder cancer and immunological pathways represent the new frontiers in biomarker discovery and possible improvement in patient selection in the era of personalized medicine.
摘要简介大约30-60%的接受过卡氏杆菌(BCG)治疗的非肌肉浸润性癌症(NMIBC)患者最终会在2年内经历疾病复发。为了避免BCG浪费,改善患者对替代疗法的咨询,提高患者的生存率和生活质量,谨慎使用BCG并准确识别可能从该疗法中受益的患者至关重要。我们总结了目前关于BCG膀胱内治疗NMIBC的预测和预后模型的文献。涵盖的领域临床病理特征是BCG反应的最强预测因素。此外,还对一些组织、血清和尿液生物标志物进行了研究。然而,它们还没有被证明足够强大,可以在日常临床中实施。因此,对肿瘤微环境的遗传和表观遗传学标志物及其特征进行了研究。Th1和Th2微环境之间的关系,以及其相关的血清和尿液生物标志物,被证明在预测对BCG治疗的反应中发挥着重要作用。专家意见没有任何一种肿瘤生物标志物被证明足够强大,足以改变临床决策。膀胱癌症遗传特征图谱和免疫途径的发现代表了个性化医学时代生物标志物发现和患者选择可能改善的新领域。
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引用次数: 1
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Expert Review of Precision Medicine and Drug Development
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