Expert Opinion on Therapeutic Targets最新文献

What is the potential of formyl peptide receptor 1 (FPR1) as a therapeutic target in human disease? 甲酰基肽受体1 （FPR1）作为人类疾病治疗靶点的潜力是什么？

IF 4.6 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2025-05-29 DOI: 10.1080/14728222.2025.2512525

Claes Dahlgren, Huamei Forsman

引用次数: 0

Emerging pathways yielding opportunities for future treatments in pancreatic ductal adenocarcinoma. 新途径为胰腺导管腺癌的未来治疗提供了机会。

IF 4.6 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2025-05-22 DOI: 10.1080/14728222.2025.2507035

Ashu Shah, Esther Johnson, Moorthy P Ponnusamy, Surinder K Batra

{"title":"Emerging pathways yielding opportunities for future treatments in pancreatic ductal adenocarcinoma.","authors":"Ashu Shah, Esther Johnson, Moorthy P Ponnusamy, Surinder K Batra","doi":"10.1080/14728222.2025.2507035","DOIUrl":"10.1080/14728222.2025.2507035","url":null,"abstract":"Introduction: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy that is often diagnosed at a late stage, resulting in poor survival rates and limited treatment options. Several factors contribute to the dismal prognosis of PDAC, including the absence of reliable biomarkers and effective therapies, as well as the complex biology of the disease.Areas covered: The pathobiology of PDAC encompasses its unique mutational landscape, desmoplastic stroma, and immune suppressive tumor microenvironment (TME). These characteristics are influenced by an intricate network of signaling pathways activated by oncogenic KRAS, DNA damage and repair machinery, metabolic adaptations, and aberrant mucin expression. This review summarizes our current understanding of these pathways to explore their potential for therapeutic vulnerabilities in PDAC. We discuss how recent efforts to elucidate these pathways have identified novel targets and treatments for this dreadful disease.Expert opinion: The complex biology of PDAC complicates the effectiveness of single therapeutic agents. To achieve durable clinical responses in patients with PDAC, it is essential to simultaneously inhibit multiple parallel or unrelated pathways. Therefore, a combination therapeutic regimen is necessary to significantly improve treatment outcomes that rely solely on biologically driven concepts. These studies suggest ways to expand our understanding of the therapeutic vulnerabilities in PDAC.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"1-18"},"PeriodicalIF":4.6,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Therapeutic targets for pulmonary arterial hypertension: insights into the emerging landscape. 肺动脉高压的治疗靶点：对新兴景观的见解。

IF 4.6 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2025-05-21 DOI: 10.1080/14728222.2025.2507034

Christopher V Flores, Stephen Y Chan

{"title":"Therapeutic targets for pulmonary arterial hypertension: insights into the emerging landscape.","authors":"Christopher V Flores, Stephen Y Chan","doi":"10.1080/14728222.2025.2507034","DOIUrl":"10.1080/14728222.2025.2507034","url":null,"abstract":"Background: Pulmonary arterial hypertension (PAH) is a progressive, life-threatening disease driven by vascular remodeling, right ventricular (RV) dysfunction, and metabolic and inflammatory dysregulation. Current therapies primarily target vasodilation to relieve symptoms but do not reverse disease progression. The recent approval of sotatercept, which modulates BMP/TGF-β signaling, marks a shift toward anti-remodeling therapies. Building on this, recent preclinical advances have identified promising therapeutic targets and potentially disease-modifying treatments.Areas covered: This review synthesizes the evolving preclinical landscape of emerging PAH therapeutic targets and drugs, highlighting innovative approaches aimed at addressing the underlying mechanisms of disease progression. Additionally, we discuss novel therapeutic strategies under development.Expert opinion: Recent advances in PAH research have identified novel therapeutic targets beyond vasodilators, including modulation of BMP/TGF-β signaling, metabolic programs, epigenetics, cancer-related signaling, the extracellular matrix, and immune pathways, among others. Sotatercept represents a significant advance in therapies that go beyond vasodilation, and long-term safety, efficacy, and durability are being assessed. Future treatment strategies will focus on precision approaches, noninvasive technologies, and regenerative biology to improve outcomes and reverse vascular remodeling.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"1-17"},"PeriodicalIF":4.6,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Multidimensional insights into squalene epoxidase drug development: in vitro mechanisms, in silico modeling, and in vivo implications. 多维洞察角鲨烯环氧化酶药物开发：体外机制，在硅模型，和体内的影响。

IF 4.6 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2025-05-08 DOI: 10.1080/14728222.2025.2500420

Ahmed A Allam, Hassan A Rudayni, Noha A Ahmed, Faris F Aba Alkhayl, Al Mokhtar Lamsabhi, Emadeldin M Kamel

{"title":"Multidimensional insights into squalene epoxidase drug development: in vitro mechanisms, in silico modeling, and in vivo implications.","authors":"Ahmed A Allam, Hassan A Rudayni, Noha A Ahmed, Faris F Aba Alkhayl, Al Mokhtar Lamsabhi, Emadeldin M Kamel","doi":"10.1080/14728222.2025.2500420","DOIUrl":"https://doi.org/10.1080/14728222.2025.2500420","url":null,"abstract":"Introduction: Squalene epoxidase (SQLE) is a pivotal enzyme in sterol biosynthesis, catalyzing the conversion of squalene to 2,3-oxidosqualene. Beyond its core role in cholesterol homeostasis, SQLE is implicated in cancer, hypercholesterolemia, and fungal infections, positioning it as a valuable therapeutic target.Areas covered: We conducted a comprehensive literature search across primary databases to gather in vitro, in silico, and in vivo evidence on SQLE. This review explores the enzyme's structural and functional features, including substrate specificity and catalytic mechanisms, and examines inhibitor interactions. Computational methods predict enzyme - inhibitor dynamics, guiding drug design, while in vivo investigations clarify SQLE's role in metabolic disorders and tumorigenesis. Challenges include drug resistance and study discrepancies, but emerging technologies, such as cryo-electron microscopy and CRISPR editing, offer new avenues for deeper exploration.Expert opinion: SQLE is an underexplored yet promising therapeutic target, with particular relevance to oxidative stress, ferroptosis, and gut microbiota research. Overcoming current barriers through advanced technologies and multidisciplinary strategies could propel SQLE-targeted treatments into clinical practice, supporting precision medicine and broader translational applications.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"1-19"},"PeriodicalIF":4.6,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143960537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The sigma-1 receptor: a mechanistically-informed therapeutic target for antidepressants. sigma-1受体：抗抑郁药物的机械信息治疗靶点。

IF 4.6 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2025-05-06 DOI: 10.1080/14728222.2025.2500424

Naomi Xiao, Liyang Yin, Kayla M Teopiz, Angela T H Kwan, Gia Han Le, Sabrina Wong, Kyle Valentino, Hayun Choi, Joshua D Rosenblat, Roger Ho, Serene Lee, Roger S McIntyre

{"title":"The sigma-1 receptor: a mechanistically-informed therapeutic target for antidepressants.","authors":"Naomi Xiao, Liyang Yin, Kayla M Teopiz, Angela T H Kwan, Gia Han Le, Sabrina Wong, Kyle Valentino, Hayun Choi, Joshua D Rosenblat, Roger Ho, Serene Lee, Roger S McIntyre","doi":"10.1080/14728222.2025.2500424","DOIUrl":"https://doi.org/10.1080/14728222.2025.2500424","url":null,"abstract":"Introduction: The mechanism of action of antidepressants is not fully ascertained. In addition to monoamines, disparate other effectors are also implicated in the molecular and cellular effects of chronic stress including neurogenesis, neurodifferentiation, and neuroplasticity. Evidence suggests sigma-1 receptors (S1Rs) as a putative target and possible mediator of antidepressant activity.Areas covered: Data from preclinical and clinical trials was synthesized from inception to August 2024. Results showed that S1Rs regulate neurotransmitter availability and release (e.g. monoamines, glutamate), and influence intracellular Ca2+ levels as well as immune inflammatory responses. The introduction of the N-Methyl-D-aspartic Acid (NMDA) antagonist/S1R agonist dextromethorphan-bupropion in August of 2022 represented the first time the Food and Drug Administration (FDA) permitted language that the hypothesized mechanism of an antidepressant involved activity at S1Rs. We also describe the physiology, pathophysiology, and function of S1Rs.Expert opinion: Sigma-1 modulation is relevant to the mechanism of action of agents currently FDA-approved in major depressive disorder (MDD) (e.g. dextromethorphan-bupropion). Modulating sigma-1 systems is fit for purpose as it relates to future therapeutic discoveries and development in depressive and other mental disorders. Whether sigma-1 modulation is uniquely relevant to targeting dimensions of psychopathology that are more difficult to treat (i.e. anhedonia) awaits determination.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"1-15"},"PeriodicalIF":4.6,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143979178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

KRAS mutations in colorectal cancer: impacts on tumor microenvironment and therapeutic implications. 结直肠癌中的KRAS突变：对肿瘤微环境的影响及其治疗意义。

IF 4.6 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2025-05-06 DOI: 10.1080/14728222.2025.2500426

Anita Emami, Pouya Mahdavi Sharif, Nima Rezaei

{"title":"KRAS mutations in colorectal cancer: impacts on tumor microenvironment and therapeutic implications.","authors":"Anita Emami, Pouya Mahdavi Sharif, Nima Rezaei","doi":"10.1080/14728222.2025.2500426","DOIUrl":"https://doi.org/10.1080/14728222.2025.2500426","url":null,"abstract":"Introduction: Despite decreasing trends in incidence, colorectal cancer (CRC) is still a major contributor to malignancy-related morbidities and mortalities. Groundbreaking advances in immunotherapies and targeted therapies benefit a subset of CRC patients, with sub-optimal outcomes. Hence, there is an unmet need to design and manufacture novel therapies, especially for advanced/metastatic disease. KRAS, the most highly mutated proto-oncogene across human malignancies, particularly in pancreatic adenocarcinoma, non-small cell lung cancer, and CRC, is an on-off switch and governs several fundamental cell signaling cascades. KRAS mutations not only propel the progression and metastasis of CRC but also critically modulate responses to targeted therapies.Areas covered: We discuss the impacts of KRAS mutations on the CRC's tumor microenvironment and describe novel strategies for targeting KRAS and its associated signaling cascades and mechanisms of drug resistance.Expert opinion: Drug development against KRAS mutations has been challenging, mainly due to structural properties (offering no appropriate binding site for small molecules), critical functions of the wild-type KRAS in non-cancerous cells, and the complex network of its downstream effector pathways (allowing malignant cells to develop resistance). Pre-clinical and early clinical data offer promises for combining KRAS inhibitors with immunotherapies and targeted therapies.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"1-23"},"PeriodicalIF":4.6,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Therapeutic potential of MK2 kinase inhibition in pathogenesis of Parkinson's disease. MK2激酶抑制在帕金森病发病机制中的治疗潜力。

IF 4.6 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2025-05-04 DOI: 10.1080/14728222.2025.2500421

Anjuman Nanda, Shivam Kumar Pandey, Rakesh Kumar Singh

引用次数: 0

Established and emerging roles of protein kinases in regulating primary sensory neurons in injury-and inflammation-associated pain. 蛋白激酶在损伤和炎症相关疼痛中调节初级感觉神经元的既定和新兴角色。

IF 4.6 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2025-04-01 Epub Date: 2025-04-13 DOI: 10.1080/14728222.2025.2489540

David Zimmermann, Michaela Kress, Istvan Nagy

{"title":"Established and emerging roles of protein kinases in regulating primary sensory neurons in injury-and inflammation-associated pain.","authors":"David Zimmermann, Michaela Kress, Istvan Nagy","doi":"10.1080/14728222.2025.2489540","DOIUrl":"10.1080/14728222.2025.2489540","url":null,"abstract":"Introduction: Recent seminal neuroscience research has significantly increased our knowledge on cellular and molecular responses of various cells in the pain pathway to peripheral nerve injuries and inflammatory processes. Transcriptomic and epigenetic analysis of primary sensory neurons (PSNs) in animal models of peripheral injuries revealed new insights into altered gene expression profiles and epigenetic modifications, which, via increasing spinal nociceptive input, lead to the development of pain. Among the various classes of molecules involved in driving differential gene expression, protein kinases, the enzymes that catalyze the phosphorylation of molecules, are emerging to control histone modification and chromatin remodeling needed for the alteration in transcriptional activity.Areas covered: Here, we focused on how protein kinases contribute to transcriptomic changes and pathways of induced reprogramming within PSNs upon peripheral nerve injury and inflammation. We conducted systematic literature search across multiple databases, including PubMed, NIH ClinicalTrials.gov portal and GEOData from 1980 to 2024 and compared protein kinase expression frequencies between publicly available RNA sequencing datasets of PSNs and investigated differences in protein kinase expression levels after peripheral nerve injury.Expert opinion: Novel findings support a new concept that protein kinases constitute regulatory hubs of reprogramming of PSNs, which offers novel analgesic approaches.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"267-280"},"PeriodicalIF":4.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Defeating kinases that promote tumorigenesis through non-catalytic functions with PROTACs - PIM kinase as an example. 击败通过非催化功能促进肿瘤发生的激酶，以PROTACs - PIM激酶为例。

IF 4.6 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2025-04-01 Epub Date: 2025-05-04 DOI: 10.1080/14728222.2025.2500418

Pedro Torres-Ayuso, John Brognard

引用次数: 0

Cellular role of CD93 and its potential as a future therapeutic target. CD93的细胞作用及其作为未来治疗靶点的潜力。

IF 4.6 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2025-04-01 Epub Date: 2025-05-02 DOI: 10.1080/14728222.2025.2500427

Maurizio Orlandini

引用次数: 0