Expert Opinion on Therapeutic Targets最新文献

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 4.6 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2025-07-21 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":"https://doi.org/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":""},"PeriodicalIF":4.6,"publicationDate":"2025-07-21","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

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 4.6 2区医学

Expert Opinion on Therapeutic Targets Pub Date : 2025-07-21 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":"https://doi.org/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":""},"PeriodicalIF":4.6,"publicationDate":"2025-07-21","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

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 4.6 2区医学

Expert Opinion on Therapeutic Targets Pub 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":"1-12"},"PeriodicalIF":4.6,"publicationDate":"2025-07-20","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

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

IF 4.6 2区医学

Expert Opinion on Therapeutic Targets Pub 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":"1-23"},"PeriodicalIF":4.6,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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 4.6 2区医学

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

Hironari Akasaka, WonJae Lee, Honami Naora

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

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

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

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