Expert Opinion on Therapeutic Targets最新文献_第4页

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 : 2025-06-01 Epub 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":"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":"345-359"},"PeriodicalIF":4.6,"publicationDate":"2025-06-01","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

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 : 2025-06-01 Epub 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":"309-326"},"PeriodicalIF":4.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12129655/pdf/","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":"OA","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 : 2025-06-01 Epub 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":"327-343"},"PeriodicalIF":4.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12129657/pdf/","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":"OA","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 : 2025-06-01 Epub 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":"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":"361-383"},"PeriodicalIF":4.6,"publicationDate":"2025-06-01","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

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

IF 4.6 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2025-04-01 Epub Date: 2025-05-12 DOI: 10.1080/14728222.2025.2500422

Marian Vincenzi, Flavia Anna Mercurio, Marilisa Leone

{"title":"Cataract-related mutations in EphA2: a survey of literature data and the relevance of the receptor Sam domain.","authors":"Marian Vincenzi, Flavia Anna Mercurio, Marilisa Leone","doi":"10.1080/14728222.2025.2500422","DOIUrl":"https://doi.org/10.1080/14728222.2025.2500422","url":null,"abstract":"Introduction: EphA2 is a receptor tyrosine kinase that is associated with various pathological conditions. Mutations in EphA2 are linked to cataract, an eye disorder manifesting as lens opacity, and representing one of the most prominent causes of blindness worldwide.Areas covered: We collected a list of cataract-related EphA2 mutations and positioned them inside the different protein domains to identify regions of the receptor that could be more likely considered targets in the 'anti-cataract' drug discovery field. Moreover, we analyzed the structural consequences these mutations could induce. A search for literature related to EphA2 and cataracts was carried out through the PubMed National Library of Medicine. Structural information on diverse EphA2 domains was obtained from the Protein Data Bank. EphA2 variants connected to cataract were checked on the databases Cat-Map and dbSNP.Expert opinion: Cataract-related mutations are gathered within diverse EphA2 domains and are abundant inside its Sam (Sterile alpha motif, EphA2-Sam) domain. Mutations affecting EphA2-Sam could disturb domain helical fold and hamper interaction with other Sam domains, eventually interfering with EphA2 cell migration activity. Identification of stabilizing small molecules targeting EphA2-Sam pathogenic variants could represent an original route to discover novel therapeutic compounds against lens opacity.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":"29 4-5","pages":"239-265"},"PeriodicalIF":4.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144063136","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

Restoring FXR expression as a novel treatment strategy in liver cancer and other liver disorders. 恢复FXR表达作为肝癌和其他肝脏疾病的新治疗策略。

IF 4.6 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2025-04-01 Epub Date: 2025-05-11 DOI: 10.1080/14728222.2025.2487465

Sosmitha Girisa, Babu Santha Aswani, Mukesh Kumar Manickasamy, Mangala Hegde, Mohammed S Alqahtani, Mohamed Abbas, Gautam Sethi, Ajaikumar B Kunnumakkara

{"title":"Restoring FXR expression as a novel treatment strategy in liver cancer and other liver disorders.","authors":"Sosmitha Girisa, Babu Santha Aswani, Mukesh Kumar Manickasamy, Mangala Hegde, Mohammed S Alqahtani, Mohamed Abbas, Gautam Sethi, Ajaikumar B Kunnumakkara","doi":"10.1080/14728222.2025.2487465","DOIUrl":"10.1080/14728222.2025.2487465","url":null,"abstract":"Introduction: Liver cancer is a leading cause of cancer-associated mortality and is often linked to preexisting liver conditions. Emerging research demonstrates FXR dysregulation, particularly its reduced expression, in the pathogenesis of liver diseases, including inflammation, fibrosis, cholestatic disorders, metabolic dysregulation, and liver cancer. Therefore, this review explores the role of FXR and its agonists in mitigating these conditions.Areas covered: This article summarizes FXR's involvement in liver disorders, primarily emphasizing on hepatic neoplasms, and examines the potential of FXR agonists in restoring FXR activity in liver diseases, thereby preventing their progression to liver cancer. The information presented is drawn from existing preclinical and clinical studies specific to each liver disorder, sourced from PubMed.Expert opinion: It is well established that FXR expression is downregulated in liver disorders, contributing to disease progression. Notably, FXR agonists have demonstrated therapeutic potential in ameliorating liver diseases, including hepatocellular carcinoma. We believe that activating or restoring FXR expression with agonists offers significant promise for the treatment of liver cancer and other liver conditions. Therefore, FXR modulation by agonists, particularly in combination with other therapeutic agents, could lead to more targeted treatments, improving efficacy while reducing side effects.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"193-221"},"PeriodicalIF":4.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763302","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

LPAR5 as a prospective therapeutic target for treating microvillus inclusion disease. LPAR5作为治疗微绒毛包涵性疾病的前瞻性治疗靶点。

IF 4.6 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2025-04-01 Epub Date: 2025-05-02 DOI: 10.1080/14728222.2025.2500416

Andreanna Burman, Izumi Kaji

引用次数: 0