Philosophical transactions of the Royal Society of London. Series B, Biological sciences最新文献_第7页

Unmet needs in functional neurological disorder related to digital healthcare. 与数字医疗保健相关的功能性神经障碍的未满足需求。

IF 4.7

Philosophical transactions of the Royal Society of London. Series B, Biological sciences Pub Date : 2026-09-17 DOI: 10.1098/rstb.2024.0460

Jon Stone

{"title":"Unmet needs in functional neurological disorder related to digital healthcare.","authors":"Jon Stone","doi":"10.1098/rstb.2024.0460","DOIUrl":"10.1098/rstb.2024.0460","url":null,"abstract":"Functional neurological disorder (FND) is a common yet historically neglected condition that presents major unmet needs across diagnosis, treatment and health service delivery. This article examines how digital healthcare could address gaps in several areas: (i) using large biobank and clinic datasets to reveal epidemiology, comorbidity, mechanisms, economic burden and possibly treatment effects; (ii) augmenting complex and time-consuming assessment processes that currently exceed clinical capacity with artificial intelligence; (iii) using digital tools to improve diagnostic precision-for example through automated tremor analysis, quantification of functional motor signs and speech recognition; (iv) improving self-management and access to therapy via online tools and telehealth programmes; (v) improving outcome measurement and existing therapy using wearables and telehealth; and (vi) new therapies such as AI-assisted therapies, biofeedback and virtual or augmented reality interventions. Finally, I discuss the risks of depersonalization, privacy breaches, therapeutic substitution, digital dependence and digital exclusion. In addition, positive therapist effects-variability in outcomes driven by the clinician rather than the intervention-remain difficult to replicate digitally. The challenge for clinicians and researchers is to ensure that technological advances humanize rather than mechanize care, harnessing digital tools to extend expertise, consistency and accessibility without eroding the therapeutic relationship at the heart of effective FND treatment. This article is part of the discussion meeting issue 'Digital healthcare for the management of functional neurological disorders'.","PeriodicalId":520748,"journal":{"name":"Philosophical transactions of the Royal Society of London. Series B, Biological sciences","volume":"381 1958","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13583494/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148984105","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}

引用次数: 0

Looking back on the history of epidermal growth factor receptor mutations in lung cancer. 肺癌表皮生长因子受体突变史的回顾。

IF 4.7

Philosophical transactions of the Royal Society of London. Series B, Biological sciences Pub Date : 2026-08-27 DOI: 10.1098/rstb.2024.0506

Roy S Herbst, Meina Wang, Katerina Politi

{"title":"Looking back on the history of epidermal growth factor receptor mutations in lung cancer.","authors":"Roy S Herbst, Meina Wang, Katerina Politi","doi":"10.1098/rstb.2024.0506","DOIUrl":"https://doi.org/10.1098/rstb.2024.0506","url":null,"abstract":"The discovery of the epidermal growth factor receptor (EGFR) represents a landmark achievement in biomedical science, laying the foundation for one of the most transformative success stories in oncology. From the early isolation of epidermal growth factor (EGF) by Stanley Cohen and colleagues to the cloning of EGFR and its identification as a receptor tyrosine kinase, these pioneering studies revealed its central role in cellular growth and proliferation and ultimately linked EGFR signalling to cancer. Early research demonstrated that aberrant EGFR activity could drive tumourigenesis, prompting the development of monoclonal antibodies and small-molecule inhibitors to block receptor activation. Initial clinical experience with first-generation tyrosine kinase inhibitors, gefitinib and erlotinib, revealed dramatic responses in select patients with non-small cell lung cancer (NSCLC), leading to the discovery of sensitizing EGFR mutations as predictive biomarkers of response. These insights ushered in the era of precision medicine in oncology, with molecular testing and targeted therapies becoming the standard of care in the diagnosis and treatment of lung cancer. Subsequent development of second- and third-generation inhibitors, including osimertinib, has further extended survival for patients with EGFR-mutant NSCLC. Despite ongoing challenges owing to drug resistance, novel therapeutic strategies and rational drug combinations continue to redefine the treatment landscape, such that the treatment of EGFR-driven lung cancer remains a paradigm for the application of precision medicine to cancer. This article is part of the discussion meeting issue 'Epidermal growth factor receptor after 40 years'.","PeriodicalId":520748,"journal":{"name":"Philosophical transactions of the Royal Society of London. Series B, Biological sciences","volume":"381 1957","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148835808","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}

引用次数: 0

Molecular mechanisms governing the action of the epidermal growth factor receptor and receptor tyrosine kinases, a personal perspective. 控制表皮生长因子受体和受体酪氨酸激酶作用的分子机制，个人观点。

IF 4.7

Philosophical transactions of the Royal Society of London. Series B, Biological sciences Pub Date : 2026-08-27 DOI: 10.1098/rstb.2024.0498

Joseph Schlessinger

引用次数: 0

Lessons in conformational signalling: non-catalytic functions of protein kinase C isozymes. 构象信号传导的教训：蛋白激酶C同工酶的非催化功能。

IF 4.7

Philosophical transactions of the Royal Society of London. Series B, Biological sciences Pub Date : 2026-08-27 DOI: 10.1098/rstb.2024.0496

Angus Cameron, Mathias Cobbaut, Veronique Calleja, Neil McDonald, Peter Parker

引用次数: 0

Functions of the EGFR in health and disease. EGFR在健康和疾病中的功能。

IF 4.7

Philosophical transactions of the Royal Society of London. Series B, Biological sciences Pub Date : 2026-08-27 DOI: 10.1098/rstb.2024.0497

Thomas Bauer, Martin Holcmann, Maria Sibilia

{"title":"Functions of the EGFR in health and disease.","authors":"Thomas Bauer, Martin Holcmann, Maria Sibilia","doi":"10.1098/rstb.2024.0497","DOIUrl":"https://doi.org/10.1098/rstb.2024.0497","url":null,"abstract":"The epidermal growth factor receptor (EGFR) is a critical mediator of cellular physiology, and its deregulation is implicated in a broad spectrum of pathological conditions, ranging from skin disorders to epithelial malignancies and brain tumours. Although lack of EGFR signalling primarily affects skin and brain development and tissue homeostasis, aberrant EGFR activation through overexpression or mutation converts the receptor into a potent oncogenic driver. This occurs particularly in human cancers such as glioblastoma, non-small-cell lung carcinoma, colorectal cancer, hepatocellular carcinoma, pancreatic ductal adenocarcinoma and head and neck squamous cell carcinoma. Genetically engineered mouse models have been instrumental in advancing our understanding of EGFR biology by elucidating mechanisms of disease initiation and progression, and by enabling the preclinical evaluation of novel therapeutic strategies. The ability to manipulate EGFR expression and activity in a spatiotemporally controlled manner in mice has allowed us to dissect its complex signalling pathways and their downstream effects, revealing unexpected functions of EGFR and enhancing its relevance for translational research. In this paper, we focus on the context-specific roles of EGFR during tumourigenesis, the therapeutic relevance of EGFR inhibition in cancer and the molecular mechanisms underlying skin toxicities associated with EGFR-targeted therapies. This article is part of the discussion meeting issue 'Epidermal growth factor receptor after 40 years'.","PeriodicalId":520748,"journal":{"name":"Philosophical transactions of the Royal Society of London. Series B, Biological sciences","volume":"381 1957","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148836176","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}

引用次数: 0

Impact of lineage-specific epidermal growth factor receptor mutations in cancer. 谱系特异性表皮生长因子受体突变对癌症的影响。

IF 4.7

Philosophical transactions of the Royal Society of London. Series B, Biological sciences Pub Date : 2026-08-27 DOI: 10.1098/rstb.2024.0501

Amy Rios, Kimberly A Jorge, Gizelle G Ramirez, Chester A Thompson, Tikvah K Hayes

引用次数: 0

The epidermal growth factor receptor-the prototypic RTK-turns 40. 表皮生长因子受体-原型rtk -满40岁。

IF 4.7

Philosophical transactions of the Royal Society of London. Series B, Biological sciences Pub Date : 2026-08-27 DOI: 10.1098/rstb.2024.0495

Tony Hunter

引用次数: 0

Targeting EGFR in lung cancer: lessons in signal transduction and treatment-induced mutagenesis. 肺癌中靶向EGFR：信号转导和治疗诱导诱变的经验教训。

IF 4.7

Philosophical transactions of the Royal Society of London. Series B, Biological sciences Pub Date : 2026-08-27 DOI: 10.1098/rstb.2024.0512

Arturo Simoni-Nieves, Marieke Van Daele, Harrison B Konsker, Yosef Yarden

{"title":"Targeting EGFR in lung cancer: lessons in signal transduction and treatment-induced mutagenesis.","authors":"Arturo Simoni-Nieves, Marieke Van Daele, Harrison B Konsker, Yosef Yarden","doi":"10.1098/rstb.2024.0512","DOIUrl":"https://doi.org/10.1098/rstb.2024.0512","url":null,"abstract":"The epidermal growth factor receptor (EGFR) plays pivotal role in cancer promotion and progression, particularly in non-small cell lung cancer (NSCLC), where activating EGFR mutations drive tumour growth. Targeted therapies, such as tyrosine kinase inhibitors (TKIs), have improved patient survival rates, but resistance inevitably develops through mechanisms ranging from secondary mutations to bypass signalling pathways and histological transformation. A key factor in resistance development is the emergence of drug-tolerant persister cells, a rare population with epigenetic alterations that precede permanent, mutation-driven resistance. These cells evade apoptosis by triggering an evolutionarily conserved survival mechanism known as SOS. The SOS process is accompanied by increased reactive oxygen species, DNA breaks, defective DNA repair and activation of mutation-inducing factors like error-prone DNA polymerases and imbalanced dNTP pools. In patients receiving TKIs, this adaptive response probably drives the formation of extrachromosomal circular DNA and various genomic aberrations, collectively resembling chromothripsis. The aberrations include not only point mutations and gene amplifications but also indels and gene fusions. To overcome resistance, new therapeutic strategies are being explored, such as fourth-generation TKIs, allosteric inhibitors, degraders and bispecific antibodies. Ongoing research into EGFR biology offers the potential to transform EGFR-positive NSCLC from a lethal disease into a chronic, manageable condition. This article is part of the discussion meeting issue 'Epidermal growth factor receptor after 40 years'.","PeriodicalId":520748,"journal":{"name":"Philosophical transactions of the Royal Society of London. Series B, Biological sciences","volume":"381 1957","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148835901","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}

引用次数: 0

Epidermal growth factor receptor dysregulation and climate change: insights into pollution-promoted lung cancer. 表皮生长因子受体失调与气候变化：对污染促进肺癌的见解。

IF 4.7

Philosophical transactions of the Royal Society of London. Series B, Biological sciences Pub Date : 2026-08-27 DOI: 10.1098/rstb.2024.0508

Taysia Nikaido-Landry, Yujia Zhang, Emilia L Lim

引用次数: 0

Ligand bias in the EGF receptor system. EGF受体系统中的配体偏置。

IF 4.7

Philosophical transactions of the Royal Society of London. Series B, Biological sciences Pub Date : 2026-08-27 DOI: 10.1098/rstb.2025.0050

Linda J Pike

{"title":"Ligand bias in the EGF receptor system.","authors":"Linda J Pike","doi":"10.1098/rstb.2025.0050","DOIUrl":"https://doi.org/10.1098/rstb.2025.0050","url":null,"abstract":"The epidermal growth factor (EGF) receptor is a canonical receptor tyrosine kinase with an extracellular ligand-binding domain, a single-pass transmembrane domain and an intracellular kinase domain. Binding of an agonist ligand leads to the dimerization of the receptor and activation of its tyrosine kinase activity. This results in autophosphorylation of the receptor on its C-terminal tail and the activation of downstream signalling pathways that mediate the intracellular effects of the agonist. The receptor binds seven different ligands. Structural studies have shown that the ligands bind to the same site on the EGF receptor and induce the formation of receptor dimers. Nonetheless, different agonists can elicit markedly different biological effects in the same cell, such as proliferation versus differentiation. This phenomenon is known as ligand bias, since the ligand biases the system to progress down one biological pathway as opposed to another. This review summarizes recent studies that have provided insight into the molecular mechanism of ligand bias in the EGF receptor system. A French translation of this abstract is available in the supplementary material. This article is part of the discussion meeting issue 'Epidermal growth factor receptor after 40 years'.","PeriodicalId":520748,"journal":{"name":"Philosophical transactions of the Royal Society of London. Series B, Biological sciences","volume":"381 1957","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148835441","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}

引用次数: 0