Expert Opinion on Therapeutic Targets最新文献_第3页

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 4.4 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2025-07-01 Epub Date: 2025-05-29 DOI: 10.1080/14728222.2025.2512525

Claes Dahlgren, Huamei Forsman

引用次数: 0

HER3 in breast cancer: molecular insights, clinical implications, and therapeutic horizons. 乳腺癌中的HER3：分子见解、临床意义和治疗前景。

IF 4.4 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2025-07-01 Epub Date: 2025-07-28 DOI: 10.1080/14728222.2025.2540355

Yakup Ergun

{"title":"HER3 in breast cancer: molecular insights, clinical implications, and therapeutic horizons.","authors":"Yakup Ergun","doi":"10.1080/14728222.2025.2540355","DOIUrl":"10.1080/14728222.2025.2540355","url":null,"abstract":"Introduction: erb-b2 receptor tyrosine kinase 3 (ERBB3/HER3) a kinase-inactive HER family receptor, significantly influences breast cancer by enhancing oncogenic signaling mainly via HER2 heterodimerization. Its role in therapy resistance marks it as a key target across subtypes, tackling a critical oncology challenge.Areas covered: This review delves into HER3's molecular structure, with its ligand-binding extracellular domain and tyrosine-rich tail activating PI3K/AKT and MAPK/ERK pathways. It examines HER3's impact on tumor progression - like invasion and metastasis - and resistance to therapies such as trastuzumab, endocrine treatments, and chemotherapy across HER2- positive, hormone receptor-positive, and triple-negative subtypes, based on extensive literature. Clinically, it assesses HER3's prognostic role, with overexpression in 30-50% of cases, and therapeutic advances, notably antibody-drug conjugates (ADCs) like patritumab deruxtecan, promising in trials.Expert opinion: HER3's therapeutic potential is transformative, with ADCs and combinations poised to redefine personalized care by improving survival in resistant cases. Its overexpression offers a strategic leverage point, yet inconsistent detection and adaptive resistance pose barriers. These demand innovative solutions, such as refined diagnostics and multi-target therapies. Given its demonstrated efficacy, HER3-targeted therapies, supported by novel therapeutic combinations and bioengineering innovations, are expected to become integral to routine clinical practice in the coming years, advancing precision oncology.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"481-489"},"PeriodicalIF":4.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144706922","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

NRG/ErbB signaling: on the trail of a molecular fingerprint in mucinous carcinoma. NRG/ErbB信号：黏液癌的分子指纹图谱。

IF 4.4 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2025-07-01 Epub Date: 2025-07-20 DOI: 10.1080/14728222.2025.2532390

Domenico Trombetta, Federico Pio Fabrizio, Massimo Di Maio, Paola Parente, Laura Melocchi, Maurizio Martini, Angelo Sparaneo, Tiziana Pia Latiano, Paolo Graziano, Giulio Rossi, Lucia Anna Muscarella

{"title":"NRG/ErbB signaling: on the trail of a molecular fingerprint in mucinous carcinoma.","authors":"Domenico Trombetta, Federico Pio Fabrizio, Massimo Di Maio, Paola Parente, Laura Melocchi, Maurizio Martini, Angelo Sparaneo, Tiziana Pia Latiano, Paolo Graziano, Giulio Rossi, Lucia Anna Muscarella","doi":"10.1080/14728222.2025.2532390","DOIUrl":"10.1080/14728222.2025.2532390","url":null,"abstract":"Introduction: Human neuregulins (NRG) are small epidermal growth factor ligands involved in the activation of ErbBs receptors. Among genomic aberrations, NRG fusions are one of the most intriguing genetic markers reported in the latest years, due to their agnostic and potentially predictive features. Mucinous carcinoma showed a higher rate of mutations in downstream effectors of NRG/ErbB activation, thus suggesting that RAS/MAPK and PIK3K/AKT pathway are involved in mucinous phenotype development and aggressiveness.Areas covered: Epidemiological data on the spectrum of all NRG/ErbBs and downstream effectors alterations in mucinous carcinoma of digestive tract, ovary, lung, and pancreato-biliary tract, as well as their correlation with respective immunological and molecular background are discussed. Peer-reviewed publications on high-quality international from PubMed and data from scientific official sites were used to update the current literature.Expert opinion: Recent scientific advances highlight the predictive and prognostic role of the NRGs/ErbBs network deregulation in cancer; anyhow its role is not well investigated in solid tumors with mucinous features. Although the mucin-rich cancers have a considerably greater rate of mutations in therapeutically critical pathways than non-mucinous ones, common mucinous pathways have not yet been found.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"423-434"},"PeriodicalIF":4.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590774","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 trap becomes the target: molecular basis for targeted inhibition of neutrophil extracellular traps in the pre-metastatic niche. 陷阱成为目标：在转移前生态位靶向抑制中性粒细胞胞外陷阱的分子基础。

IF 4.4 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2025-07-01 Epub Date: 2025-07-11 DOI: 10.1080/14728222.2025.2532387

Hironari Akasaka, WonJae Lee, Honami Naora

引用次数: 0

Macrophage migration inhibitory factor (MIF): can functional insights pave the way for future therapeutics in cardiovascular diseases? 巨噬细胞迁移抑制因子（MIF）：能否为心血管疾病的未来治疗铺平道路？

IF 4.4 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2025-07-01 Epub Date: 2025-07-27 DOI: 10.1080/14728222.2025.2537414

Tatyana Storozhenko, Olga Petyunina, Alexander Berezin, Mykola Kopytsya

{"title":"Macrophage migration inhibitory factor (MIF): can functional insights pave the way for future therapeutics in cardiovascular diseases?","authors":"Tatyana Storozhenko, Olga Petyunina, Alexander Berezin, Mykola Kopytsya","doi":"10.1080/14728222.2025.2537414","DOIUrl":"10.1080/14728222.2025.2537414","url":null,"abstract":"Introduction: Macrophage migration inhibitory factor (MIF) is a multifunctional cytokine involved in immune regulation, inflammation, and tissue homeostasis. Elevated MIF levels contribute to the progression of various cardiovascular diseases (CVDs), making it an attractive therapeutic target. However, the pleiotropic nature and complexity of MIF context-dependent effects pose significant challenges for clinical translation, but also offer unique opportunities to develop new precision medicine-based tools.Areas covered: This review summarizes the biological functions of MIF and its homolog MIF-2 in CVD pathogenesis, along with the current landscape of therapies targeting MIF. We highlight recent preclinical findings, discuss ongoing controversies surrounding MIF's dual roles, and explore the potential of personalized approaches.Expert opinion: MIF represents a promising yet complex target in cardiovascular medicine. Future success in clinical application will depend on the development of highly selective modulators, integration of patient stratification strategies and MIF-based interventions as part of multimodal cardiovascular care.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":"29 7","pages":"415-421"},"PeriodicalIF":4.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728975","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

Improving therapeutic strategies for triple-negative breast cancer: synergistic effects of DKC1 inhibition and paclitaxel. 改善三阴性乳腺癌的治疗策略：DKC1抑制和紫杉醇的协同作用。

IF 4.4 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2025-07-01 Epub Date: 2025-07-27 DOI: 10.1080/14728222.2025.2537416

Roman Vilarullo, María Del Pilar Casco, María Candelaria Mares Ahlers, Vanesa Gottifredi, Lara Balcone, Julian Maggio, Diego Luis Mengual Gomez, Daniel Eduardo Gomez, Romina Gabriela Armando

{"title":"Improving therapeutic strategies for triple-negative breast cancer: synergistic effects of DKC1 inhibition and paclitaxel.","authors":"Roman Vilarullo, María Del Pilar Casco, María Candelaria Mares Ahlers, Vanesa Gottifredi, Lara Balcone, Julian Maggio, Diego Luis Mengual Gomez, Daniel Eduardo Gomez, Romina Gabriela Armando","doi":"10.1080/14728222.2025.2537416","DOIUrl":"10.1080/14728222.2025.2537416","url":null,"abstract":"Background: Paclitaxel (PTX) is a standard treatment for triple-negative breast cancer (TNBC), but its effectiveness is often compromised by toxicity at therapeutic doses. Dyskerin pseudouridine synthase 1 (DKC1), a telomerase subunit, is overexpressed in TNBC and associated with poor prognosis. This study investigates whether combining PTX with R1D2-10, a novel DKC1 inhibitor developed by our group, enhances cytotoxicity while reducing required PTX dosages.Research design and methods: In vitro assays were conducted using MDA-MB-231 and MDA-MB-468 TNBC cell lines, treated with R1D2-10, PTX or their combination. Cytotoxicity, drug synergy, clonogenic capacity, cell cycle distribution, apoptosis, and DNA damage markers were evaluated to assess efficacy and mechanism of action.Results: The combination demonstrated synergistic effects, showing dose-dependent cytotoxicity and achieving a Dose Reduction Index (DRI) exceeding 3. Furthermore, the treatment significantly reduced colony formation and induced a rise in cell cycle population, both at the G2/M and Sub-G1 phases. These effects are supported by increased apoptosis and gene expression markers for cell cycle arrest, without evidence of replication stress or DNA damage.Conclusions: Combining R1D2-10 with PTX may provide an effective therapeutic strategy to reduce dose-related toxicity while enhancing chemotherapy effects in TNBC. Further, in vivo studies are needed to validate these findings.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"491-504"},"PeriodicalIF":4.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674215","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

Targeting CDK2 and other novel cell cycle targets for breast cancer therapy. 靶向CDK2和其他新的细胞周期靶点用于乳腺癌治疗。

IF 4.4 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2025-07-01 Epub Date: 2025-07-26 DOI: 10.1080/14728222.2025.2537412

Mei-Kuang Chen, Linjie Luo, Nicole Massoumi, Khandan Keyomarsi

{"title":"Targeting CDK2 and other novel cell cycle targets for breast cancer therapy.","authors":"Mei-Kuang Chen, Linjie Luo, Nicole Massoumi, Khandan Keyomarsi","doi":"10.1080/14728222.2025.2537412","DOIUrl":"10.1080/14728222.2025.2537412","url":null,"abstract":"Introduction: The dysregulation of cyclin-dependent kinases (CDKs) is a key driver of cancer progression, making them attractive therapeutic targets. In CDK4/6 inhibitor (CDK4/6i)-resistant breast cancer, targeting CDK2 offers a promising approach. CDK2 is frequently hyperactivated due to cyclin E1 overexpression or retinoblastoma protein loss, acting as a mechanism that sustains proliferation despite CDK4/6 inhibition. CDK2 inhibitors (CDK2i) show strong anti-tumor activity, particularly in combination with CDK4/6i or immune checkpoint inhibitors.Areas covered: This review explores the biological roles of CDK2 and its regulatory mechanisms. The review highlights the latest advancements in CDK2i, their mechanisms of action, and their potential in combination strategies with CDK4/6i, chemotherapy, and immunotherapies. Additionally, it examines other emerging targets, such as CDK7 and CDK5, which contribute to transcriptional regulation and immune evasion, respectively.Expert opinion: Future research should focus on biomarker-driven patient selection, optimizing CDK2i combinations, and expanding CDK7 inhibitor applications. Integrating multi-omics profiling can refine patient stratification, while combination strategies with chemotherapy, DNA damaging agents, and immunotherapies may enhance efficacy. CDK7 inhibitors could also complement CDK2 targeting by modulating resistance mechanisms. Personalized, adaptive treatment approaches will be key to maximizing the clinical impact of CDK2 and CDK7 inhibitors in breast cancer therapy.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"435-456"},"PeriodicalIF":4.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682245","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

Metabolic hallmarks of trastuzumab resistance. 曲妥珠单抗耐药的代谢特征。

IF 4.4 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2025-07-01 Epub Date: 2025-07-16 DOI: 10.1080/14728222.2025.2532394

Begoña Martin-Castillo, Sara Verdura, Àngela Llop-Hernández, Ruth Lupu, Elisabet Cuyàs, Javier A Menendez

{"title":"Metabolic hallmarks of trastuzumab resistance.","authors":"Begoña Martin-Castillo, Sara Verdura, Àngela Llop-Hernández, Ruth Lupu, Elisabet Cuyàs, Javier A Menendez","doi":"10.1080/14728222.2025.2532394","DOIUrl":"10.1080/14728222.2025.2532394","url":null,"abstract":"Introduction: The HER2-targeted monoclonal antibody trastuzumab has significantly improved the survival of patients with HER2-positive breast cancer (HER2+ BC) in both early and metastatic disease. Therapeutic resistance remains an inevitable challenge in the advanced setting, ultimately limiting the long-term efficacy of trastuzumab. Numerous mechanisms of trastuzumab resistance and response heterogeneity have been described, most involving alterations in HER2 receptor levels and reactivation of HER2 downstream signaling. However, the growing number of metabolic escape routes that allow HER2+ BC cells to evade HER2 inhibition have received little attention.Areas covered: We comprehensively review the metabolic strategies that HER2+ BC cells adopt to enable trastuzumab resistance, grouping them into a structured classification that takes into account their functional nature, namely: (1) metabolic reprogramming - how cells maintain an adequate supply of energy and biosynthetic precursors to survive, grow and proliferate despite HER2 inhibition; (2) adaptive stress response - how cells increase their resilience to survive trastuzumab-induced stress and damage; and (3) metabolic-signaling crosstalk - how key survival pathways redirect metabolism to reinforce trastuzumab resistance feedback loops.Expert opinion: The metabolic hallmarks of trastuzumab resistance may help to identify high-quality predictive biomarkers and to rationally develop optimized therapeutic strategies to counteract trastuzumab resistance metabolically.","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"457-479"},"PeriodicalIF":4.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12434138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607881","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 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 : 2025-06-01 Epub Date: 2025-05-04 DOI: 10.1080/14728222.2025.2500421

Anjuman Nanda, Shivam Kumar Pandey, Rakesh Kumar Singh

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 : 2025-06-01 Epub 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":"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":"385-403"},"PeriodicalIF":4.6,"publicationDate":"2025-06-01","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