Pub Date : 2021-01-01Epub Date: 2020-12-14DOI: 10.1080/23808993.2021.1857237
Jeffrey A Sparks
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
{"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":"6 3","pages":"147-149"},"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}
Pub Date : 2021-01-01Epub Date: 2020-10-28DOI: 10.1080/23808993.2021.1840273
Mario C Deng
Introduction: 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.
Areas covered: 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.
Expert opinion: 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.
{"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":"6 1","pages":"51-63"},"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}
Pub Date : 2021-01-01DOI: 10.1080/23808993.2021.1854611
Michael H Roehrl, Victor B Roehrl, Julia Y Wang
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?
{"title":"Proteome-based pathology: the next frontier in precision medicine.","authors":"Michael H Roehrl, Victor B Roehrl, 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":"6 1","pages":"1-4"},"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}
Pub Date : 2021-01-01Epub Date: 2021-08-11DOI: 10.1080/23808993.2021.1938545
Jeffrey Zhao, Carlos Galvez, Kathryn Eby Beckermann, Douglas B Johnson, Jeffrey A Sosman
Introduction: NRAS was the first mutated oncogene identified in melanoma and is currently the second most common driver mutation in this malignancy. For patients with NRASmutant advanced stage melanoma refractory to immunotherapy or with contraindications to immune-based regimens, there are few therapeutic options including low-efficacy chemotherapy regimens and binimetinib monotherapy. Here, we review recent advances in preclinical studies of molecular targets for NRAS mutant melanoma as well as the failures and successes of early-phase clinical trials. While there are no targeted therapies for NRAS-driven melanoma, there is great promise in approaches combining MEK inhibition with inhibitors of the focal adhesion kinase (FAK), inhibitors of autophagy pathways, and pan-RAF inhibitors.
Areas covered: This review surveys new developments in all aspects of disease pathogenesis and potential treatment - including those that have failed, stalled, or progressed through various phases of preclinical and clinical development.
Expert opinion: There are no currently approved targeted therapies for BRAF wild-type melanoma patients harboring NRAS driver mutations though an array of agents are in early phase clinical trials. The diverse strategies taken exploit combined MAP kinase signaling blockade with inhibition of cell cycle mediators, inhibition of the autophagy pathway, and alteration of kinases involved in actin cytoskeleton signaling. Future advances of developmental therapeutics into late stage trials may yield new options beyond immunotherapy for patients with advanced stage disease and NRAS mutation status.
{"title":"Novel insights into the pathogenesis and treatment of NRAS mutant melanoma.","authors":"Jeffrey Zhao, Carlos Galvez, Kathryn Eby Beckermann, Douglas B Johnson, Jeffrey A Sosman","doi":"10.1080/23808993.2021.1938545","DOIUrl":"10.1080/23808993.2021.1938545","url":null,"abstract":"<p><strong>Introduction: </strong>NRAS was the first mutated oncogene identified in melanoma and is currently the second most common driver mutation in this malignancy. For patients with NRAS<sup>mutant</sup> advanced stage melanoma refractory to immunotherapy or with contraindications to immune-based regimens, there are few therapeutic options including low-efficacy chemotherapy regimens and binimetinib monotherapy. Here, we review recent advances in preclinical studies of molecular targets for NRAS mutant melanoma as well as the failures and successes of early-phase clinical trials. While there are no targeted therapies for NRAS-driven melanoma, there is great promise in approaches combining MEK inhibition with inhibitors of the focal adhesion kinase (FAK), inhibitors of autophagy pathways, and pan-RAF inhibitors.</p><p><strong>Areas covered: </strong>This review surveys new developments in all aspects of disease pathogenesis and potential treatment - including those that have failed, stalled, or progressed through various phases of preclinical and clinical development.</p><p><strong>Expert opinion: </strong>There are no currently approved targeted therapies for BRAF wild-type melanoma patients harboring NRAS driver mutations though an array of agents are in early phase clinical trials. The diverse strategies taken exploit combined MAP kinase signaling blockade with inhibition of cell cycle mediators, inhibition of the autophagy pathway, and alteration of kinases involved in actin cytoskeleton signaling. Future advances of developmental therapeutics into late stage trials may yield new options beyond immunotherapy for patients with advanced stage disease and NRAS mutation status.</p>","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":"6 4","pages":"281-294"},"PeriodicalIF":1.2,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415440/pdf/nihms-1714276.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9349969","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}
Pub Date : 2020-12-31DOI: 10.1080/23808993.2021.1862648
A. Pye, S. Khan, T. Whitehouse, A. Turner
ABSTRACT Introduction: There is currently no specific treatment for liver disease due to alpha-1 antitrypsin deficiency (AATD) other than care applied for other liver diseases including transplantation. This review describes the personalized approaches to liver disease in AATD, and the current stage of development of new therapeutic agents. Areas covered: We review the pathology, presentation and progression of AATD liver disease and the approaches being taken to understand the natural history of the disease to aid future therapeutic advances. Peri- and post-transplant care is described and we highlight the reasons that alternative approaches to avoid the need for liver transplantation are being explored. The role of patient selection for new therapies is addressed as this is likely to be of paramount importance to achieve better outcomes. Expert opinion: Treatments directed at both liver, and lung and liver combined, are now being trialed in patients with AATD. The next 5–10 years may determine a more reliable noninvasive measurement of liver fibrosis, together with predictors of who is most likely to progress and develop cirrhosis. Personalized approaches could optimize when and how to effectively manage an individual with a cost-effective treatment and avoid progression to liver transplantation.
{"title":"Personalizing liver targeted treatments and transplantation for patients with alpha-1 antitrypsin deficiency","authors":"A. Pye, S. Khan, T. Whitehouse, A. Turner","doi":"10.1080/23808993.2021.1862648","DOIUrl":"https://doi.org/10.1080/23808993.2021.1862648","url":null,"abstract":"ABSTRACT Introduction: There is currently no specific treatment for liver disease due to alpha-1 antitrypsin deficiency (AATD) other than care applied for other liver diseases including transplantation. This review describes the personalized approaches to liver disease in AATD, and the current stage of development of new therapeutic agents. Areas covered: We review the pathology, presentation and progression of AATD liver disease and the approaches being taken to understand the natural history of the disease to aid future therapeutic advances. Peri- and post-transplant care is described and we highlight the reasons that alternative approaches to avoid the need for liver transplantation are being explored. The role of patient selection for new therapies is addressed as this is likely to be of paramount importance to achieve better outcomes. Expert opinion: Treatments directed at both liver, and lung and liver combined, are now being trialed in patients with AATD. The next 5–10 years may determine a more reliable noninvasive measurement of liver fibrosis, together with predictors of who is most likely to progress and develop cirrhosis. Personalized approaches could optimize when and how to effectively manage an individual with a cost-effective treatment and avoid progression to liver transplantation.","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":"6 1","pages":"65 - 78"},"PeriodicalIF":1.2,"publicationDate":"2020-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23808993.2021.1862648","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43289188","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}
Pub Date : 2020-12-24DOI: 10.1080/23808993.2021.1838275
Manish Thapar, S. Rudnick, H. Bonkovsky
ABSTRACT Introduction Acute hepatic porphyrias (AHPs) are a group of rare genetic disorders that affect the enzymes of the heme biosynthetic pathway. Patients have a varied presentation, but attacks of severe abdominal pain are the cardinal feature. Until recently, IV hemin was the only definitive treatment option available. Areas covered We summarize salient features of AHP and the work leading to clinical studies of givosiran and to its approval by the US FDA and the EMA. Givosiran is a novel siRNA therapeutic agent that targets hepatic 5-aminolevulinic acid (ALA) synthase-1, the first and rate limiting enzyme in the heme biosynthetic pathway. It has been effective in decreasing the levels of hepatic ALA synthase-1 mRNA, levels of ALA, which likely is the chief neurotoxin, and the composite attack rates in patients with AHP. The drug can cause elevated liver enzymes, elevations in serum creatinine, and injection site reactions. Single doses, given to asymptomatic persons with AIP who are chronic high excretors of ALA and porphobilinogen, caused decreases in CYP1A2 and CYP2D6 activity, raising concern for drug interactions. Expert opinion Givosiran is expensive; insurance plans are likely to limit its availability to patients with well-documented AHP and frequent and severe acute attacks.
{"title":"Givosiran, a novel treatment for acute hepatic porphyrias","authors":"Manish Thapar, S. Rudnick, H. Bonkovsky","doi":"10.1080/23808993.2021.1838275","DOIUrl":"https://doi.org/10.1080/23808993.2021.1838275","url":null,"abstract":"ABSTRACT Introduction Acute hepatic porphyrias (AHPs) are a group of rare genetic disorders that affect the enzymes of the heme biosynthetic pathway. Patients have a varied presentation, but attacks of severe abdominal pain are the cardinal feature. Until recently, IV hemin was the only definitive treatment option available. Areas covered We summarize salient features of AHP and the work leading to clinical studies of givosiran and to its approval by the US FDA and the EMA. Givosiran is a novel siRNA therapeutic agent that targets hepatic 5-aminolevulinic acid (ALA) synthase-1, the first and rate limiting enzyme in the heme biosynthetic pathway. It has been effective in decreasing the levels of hepatic ALA synthase-1 mRNA, levels of ALA, which likely is the chief neurotoxin, and the composite attack rates in patients with AHP. The drug can cause elevated liver enzymes, elevations in serum creatinine, and injection site reactions. Single doses, given to asymptomatic persons with AIP who are chronic high excretors of ALA and porphobilinogen, caused decreases in CYP1A2 and CYP2D6 activity, raising concern for drug interactions. Expert opinion Givosiran is expensive; insurance plans are likely to limit its availability to patients with well-documented AHP and frequent and severe acute attacks.","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":"6 1","pages":"9 - 18"},"PeriodicalIF":1.2,"publicationDate":"2020-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23808993.2021.1838275","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43244105","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}
Pub Date : 2020-12-23DOI: 10.1080/23808993.2021.1863781
J. Gschwend, K. Miller
ABSTRACT Introduction: New-generation hormonal therapies such as abiraterone acetate (AA) in combination with prednisone or prednisolone (AAP) have improved the overall survival (OS) in patients with chemotherapy-pretreated and naïve metastatic castration-resistant prostate cancer (mCRPC). More recently, AAP has demonstrated efficacy in newly diagnosed high-risk metastatic hormone-sensitive prostate cancer (mHSPC) and has received expanded approval for this indication. Areas covered: This review is intended to provide a thorough overview of AA as the first-in-class and only currently approved steroid 17α-hydroxylase/C17,20-lyase (CYP17) inhibitor for prostate cancer. To the best of our knowledge, this is the most comprehensive review of AAP that covers all three indications: mCRPC in the pre- and post-chemotherapy setting, and mHSPC. We describe, among other things, the mechanism of action of AA and review data on its efficacy and safety from phase 1, 2 and the pivotal phase 3 clinical trials that support its use in the mentioned approved indications. Expert opinion: AAP has been established over the past 10 years and was added to the WHO list of essential medicines in 2019 through an evidence-based selection process in which quality, safety, efficacy, and cost-effectiveness are key criteria, highlighting its role in the current therapeutic landscape of prostate cancer management.
{"title":"Abiraterone acetate plus prednisone/prednisolone in hormone-sensitive and castration-resistant metastatic prostate cancer","authors":"J. Gschwend, K. Miller","doi":"10.1080/23808993.2021.1863781","DOIUrl":"https://doi.org/10.1080/23808993.2021.1863781","url":null,"abstract":"ABSTRACT Introduction: New-generation hormonal therapies such as abiraterone acetate (AA) in combination with prednisone or prednisolone (AAP) have improved the overall survival (OS) in patients with chemotherapy-pretreated and naïve metastatic castration-resistant prostate cancer (mCRPC). More recently, AAP has demonstrated efficacy in newly diagnosed high-risk metastatic hormone-sensitive prostate cancer (mHSPC) and has received expanded approval for this indication. Areas covered: This review is intended to provide a thorough overview of AA as the first-in-class and only currently approved steroid 17α-hydroxylase/C17,20-lyase (CYP17) inhibitor for prostate cancer. To the best of our knowledge, this is the most comprehensive review of AAP that covers all three indications: mCRPC in the pre- and post-chemotherapy setting, and mHSPC. We describe, among other things, the mechanism of action of AA and review data on its efficacy and safety from phase 1, 2 and the pivotal phase 3 clinical trials that support its use in the mentioned approved indications. Expert opinion: AAP has been established over the past 10 years and was added to the WHO list of essential medicines in 2019 through an evidence-based selection process in which quality, safety, efficacy, and cost-effectiveness are key criteria, highlighting its role in the current therapeutic landscape of prostate cancer management.","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":"6 1","pages":"41 - 49"},"PeriodicalIF":1.2,"publicationDate":"2020-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23808993.2021.1863781","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46163826","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}
Pub Date : 2020-12-17DOI: 10.1080/23808993.2021.1855075
T. Naito, H. Shiraishi, Y. Fujiwara
ABSTRACT Introduction: Immune checkpoint inhibitors, monoclonal antibodies directed against programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1), have broadened treatment options for patients with non-small cell lung cancer (NSCLC). Durvalumab is a selective, high-affinity, human IgG1 monoclonal anti-PD-L1 antibody that blocks interactions of PD-L1 with PD-1 and CD80. Areas covered: We reviewed clinical data supporting the use of durvalumab as a monotherapy and combination therapy for the treatment of locally advanced and advanced NSCLC. Expert commentary: Durvalumab as a monotherapy or combination therapy has shown well-tolerated safety profiles for NSCLC in several trials. Durvalumab monotherapy in advanced NSCLC patients with PD-L1 ≥ 25% as later line (ATLANTIC study) therapy led to clinically meaningful improvements compared to standard of care. Combination therapy comprising durvalumab plus tremelimumab for advanced NSCLC did not show clinical efficacy in three phase III trials. Durvalumab administered after chemoradiotherapy in stage III NSCLC (PACIFIC study) significantly improved progression-free survival and overall survival. This result has led to approval of durvalumab for patients with locally advanced NSCLC as the standard of care. Ongoing trials provide insight into how durvalumab fits into the rapidly evolving therapeutic landscape for locally advanced or advanced NSCLC.
{"title":"Durvalumab for the treatment of PD-L1 non-small cell lung cancer","authors":"T. Naito, H. Shiraishi, Y. Fujiwara","doi":"10.1080/23808993.2021.1855075","DOIUrl":"https://doi.org/10.1080/23808993.2021.1855075","url":null,"abstract":"ABSTRACT Introduction: Immune checkpoint inhibitors, monoclonal antibodies directed against programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1), have broadened treatment options for patients with non-small cell lung cancer (NSCLC). Durvalumab is a selective, high-affinity, human IgG1 monoclonal anti-PD-L1 antibody that blocks interactions of PD-L1 with PD-1 and CD80. Areas covered: We reviewed clinical data supporting the use of durvalumab as a monotherapy and combination therapy for the treatment of locally advanced and advanced NSCLC. Expert commentary: Durvalumab as a monotherapy or combination therapy has shown well-tolerated safety profiles for NSCLC in several trials. Durvalumab monotherapy in advanced NSCLC patients with PD-L1 ≥ 25% as later line (ATLANTIC study) therapy led to clinically meaningful improvements compared to standard of care. Combination therapy comprising durvalumab plus tremelimumab for advanced NSCLC did not show clinical efficacy in three phase III trials. Durvalumab administered after chemoradiotherapy in stage III NSCLC (PACIFIC study) significantly improved progression-free survival and overall survival. This result has led to approval of durvalumab for patients with locally advanced NSCLC as the standard of care. Ongoing trials provide insight into how durvalumab fits into the rapidly evolving therapeutic landscape for locally advanced or advanced NSCLC.","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":"6 1","pages":"95 - 105"},"PeriodicalIF":1.2,"publicationDate":"2020-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23808993.2021.1855075","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47734184","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}
Pub Date : 2020-12-14DOI: 10.1080/23808993.2021.1858053
A. Ariani, N. Sverzellati, Andrea Becciolni, G. Milanese, Mario Silva
ABSTRACT Introduction: Interstitial lung disease (ILD) is the main cause of mortality in systemic sclerosis (SSc). Methods stratifying the prognosis of SSc-ILD are lacking in clinical practice. The quantification of ILD provides a paramount contribution to establishing prognosis and may assist in tailored treatment. Areas covered: In this review, we provide an overview of the main quantitative methods implemented in SSc-ILD (semi-quantitative assessment, volumetric, parametric, and textural quantitative evaluation). Even if they are different one from another, all of them have a prognostic value as they predict mortality as well as radiological and functional worsening. Expert opinion: Semi-quantitative rating of CT images (sQCT) is now the gold standard for SSc-ILD patient assessment and stratification. Furthermore, there are many software available for quantification objective quantification, and classification of ILD. These tools are barely burdened by inter- intra-reader variability and they are suitable for both trial and clinical application. It is therefore expected that in the next few years a better stratification of patients will be achieved by these tools, allowing to recognize patients with the worst prognosis. This, together with the availability of different treatments for pulmonary fibrosis, makes it possible to develop precision medicine also in the field of SSc-ILD.
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Pub Date : 2020-11-16DOI: 10.1080/23808993.2020.1842731
B. Siaton, Beth H. Hogans, M. Hochberg
{"title":"Precision medicine in osteoarthritis: not yet ready for prime time","authors":"B. Siaton, Beth H. Hogans, M. Hochberg","doi":"10.1080/23808993.2020.1842731","DOIUrl":"https://doi.org/10.1080/23808993.2020.1842731","url":null,"abstract":"","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":"6 1","pages":"5 - 8"},"PeriodicalIF":1.2,"publicationDate":"2020-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23808993.2020.1842731","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41806953","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}
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