{"title":"横纹肌肉瘤:显微镜下分子疗法的发展。","authors":"Peter J Houghton, Mary-Ann Bjornsti","doi":"10.1080/14728222.2025.2551106","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Rhabdomyosarcoma (RMS), predominantly diagnosed in children, represents 3% of the pediatric solid tumors. RMS has characteristics of skeletal muscle, although the cell of origin remains controversial. Cytotoxic therapeutics, radiation treatment and surgery remain the standard of care; however, outcomes for advanced disease have not changed for several decades. Major research advances over the past two decades have defined molecular subtypes and driver mutations that could provide new therapeutic targets.</p><p><strong>Areas covered: </strong>Due to the small number of patients diagnosed with RMS, progress in testing novel agents has been slow and, although many drugs with 'molecular targets' have been identified as 'active' in preclinical models, there remains a lack of standardization for evaluating efficacy. Molecular therapeutics identified in model systems include kinase inhibitors, antibody-drug conjugates (ADCs), chimeric antigen receptor T-cells (CAR T-cells), and drugs that target the genetic/epigenetic drivers of RMS. More recently, immune checkpoint inhibitors have entered clinical trials.</p><p><strong>Expert opinion: </strong>RMS represents a set of diseases with unique molecular drivers that will each necessitate the development of targeted therapeutics. For efficient development of effective treatments, novel approaches to preclinical testing and standardization of efficacy assessments need to be developed in conjunction with molecularly guided clinical trials in patients earlier in their disease before drug resistance develops.</p>","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"537-555"},"PeriodicalIF":4.4000,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Rhabdomyosarcoma: development of molecular therapeutics under the microscope.\",\"authors\":\"Peter J Houghton, Mary-Ann Bjornsti\",\"doi\":\"10.1080/14728222.2025.2551106\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Rhabdomyosarcoma (RMS), predominantly diagnosed in children, represents 3% of the pediatric solid tumors. RMS has characteristics of skeletal muscle, although the cell of origin remains controversial. Cytotoxic therapeutics, radiation treatment and surgery remain the standard of care; however, outcomes for advanced disease have not changed for several decades. Major research advances over the past two decades have defined molecular subtypes and driver mutations that could provide new therapeutic targets.</p><p><strong>Areas covered: </strong>Due to the small number of patients diagnosed with RMS, progress in testing novel agents has been slow and, although many drugs with 'molecular targets' have been identified as 'active' in preclinical models, there remains a lack of standardization for evaluating efficacy. Molecular therapeutics identified in model systems include kinase inhibitors, antibody-drug conjugates (ADCs), chimeric antigen receptor T-cells (CAR T-cells), and drugs that target the genetic/epigenetic drivers of RMS. More recently, immune checkpoint inhibitors have entered clinical trials.</p><p><strong>Expert opinion: </strong>RMS represents a set of diseases with unique molecular drivers that will each necessitate the development of targeted therapeutics. For efficient development of effective treatments, novel approaches to preclinical testing and standardization of efficacy assessments need to be developed in conjunction with molecularly guided clinical trials in patients earlier in their disease before drug resistance develops.</p>\",\"PeriodicalId\":12185,\"journal\":{\"name\":\"Expert Opinion on Therapeutic Targets\",\"volume\":\" \",\"pages\":\"537-555\"},\"PeriodicalIF\":4.4000,\"publicationDate\":\"2025-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Expert Opinion on Therapeutic Targets\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/14728222.2025.2551106\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/8/27 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Expert Opinion on Therapeutic Targets","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/14728222.2025.2551106","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/8/27 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Rhabdomyosarcoma: development of molecular therapeutics under the microscope.
Introduction: Rhabdomyosarcoma (RMS), predominantly diagnosed in children, represents 3% of the pediatric solid tumors. RMS has characteristics of skeletal muscle, although the cell of origin remains controversial. Cytotoxic therapeutics, radiation treatment and surgery remain the standard of care; however, outcomes for advanced disease have not changed for several decades. Major research advances over the past two decades have defined molecular subtypes and driver mutations that could provide new therapeutic targets.
Areas covered: Due to the small number of patients diagnosed with RMS, progress in testing novel agents has been slow and, although many drugs with 'molecular targets' have been identified as 'active' in preclinical models, there remains a lack of standardization for evaluating efficacy. Molecular therapeutics identified in model systems include kinase inhibitors, antibody-drug conjugates (ADCs), chimeric antigen receptor T-cells (CAR T-cells), and drugs that target the genetic/epigenetic drivers of RMS. More recently, immune checkpoint inhibitors have entered clinical trials.
Expert opinion: RMS represents a set of diseases with unique molecular drivers that will each necessitate the development of targeted therapeutics. For efficient development of effective treatments, novel approaches to preclinical testing and standardization of efficacy assessments need to be developed in conjunction with molecularly guided clinical trials in patients earlier in their disease before drug resistance develops.
期刊介绍:
The journal evaluates molecules, signalling pathways, receptors and other therapeutic targets and their potential as candidates for drug development. Articles in this journal focus on the molecular level and early preclinical studies. Articles should not include clinical information including specific drugs and clinical trials.
The Editors welcome:
Reviews covering novel disease targets at the molecular level and information on early preclinical studies and their implications for future drug development.
Articles should not include clinical information including specific drugs and clinical trials.
Original research papers reporting results of target selection and validation studies and basic mechanism of action studies for investigative and marketed drugs.
The audience consists of scientists, managers and decision makers in the pharmaceutical industry, academic researchers working in the field of molecular medicine and others closely involved in R&D.