Molecular Diagnosis & Therapy最新文献

{"title":"The Current Status of Radionuclide Tumor Targeting Diagnosis and Therapy Based on FAP-2286: From Preclinical Studies to Clinical Application.","authors":"Huajun Liu, Zhen Yang, Junzheng Wang, Chunyin Zhang","doi":"10.1007/s40291-026-00830-z","DOIUrl":"10.1007/s40291-026-00830-z","url":null,"abstract":"<p><p>In recent years, fibroblast activation protein (FAP) has demonstrated significant potential in oncology, and the development of FAP-targeted therapeutic agents has increasingly become a key research focus in the fields of molecular imaging and radionuclide therapy. Among these, FAP inhibitor (FAPI)-based small molecules have demonstrated favorable pharmacokinetics and imaging potential, showing promising potential in the diagnosis and treatment of tumors. As a peptide-based radiopharmaceutical derived from structural optimization of FAPI, FAP-2286 consists of a FAP-specific binding peptide conjugated to a DOTA chelator. It not only preserves the high affinity and favorable imaging characteristics of small-molecule FAPI tracers but also markedly prolongs tumor retention, thereby enabling both diagnostic and therapeutic applications. Preclinical and early clinical studies have shown encouraging results, characterized by prolonged in vivo retention and a favorable safety profile, supporting its use as a theranostic agent. This review provides a comprehensive overview of the current literature on FAP-2286, from preclinical development to clinical translation, highlighting its diagnostic value, the status of FAP-targeted radionuclide therapy, and the challenges and opportunities in advancing FAP-based theranostics.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"281-293"},"PeriodicalIF":5.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146047310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing Medulloblastoma Treatment: Molecular Mechanisms, Drug Repurposing, and Precision Therapies.","authors":"Mohammed A Abdel-Rasol, Wael M El-Sayed","doi":"10.1007/s40291-025-00817-2","DOIUrl":"10.1007/s40291-025-00817-2","url":null,"abstract":"<p><p>Medulloblastomas are the most common malignant pediatric brain tumors, representing approximately 20% of the central nervous system cancers in children. These tumors are highly heterogeneous and classified into four molecular subgroups-WNT, SHH, Group 3, and Group 4-each with distinct genetic and epigenetic profiles that influence tumor behavior, therapeutic response, and patient outcomes. Advances in molecular diagnostics have improved the subclassification of medulloblastomas, yet treatment outcomes for high-risk subtypes, particularly Group 3, remain poor, with current modalities often associated with severe long-term neurocognitive and systemic toxicities. Effective drug delivery across the blood-brain barrier remains a major hurdle, limiting the clinical efficacy of targeted therapies. Drug repurposing offers a promising strategy to accelerate treatment availability by utilizing US Food and Drug Administration-approved agents, including niclosamide, itraconazole, and arsenic trioxide, to target critical oncogenic pathways and overcome therapeutic resistance. However, challenges such as limited blood-brain barrier penetration and the lack of pediatric-specific pharmacokinetic data persist. Future research should focus on integrating comprehensive molecular profiling to guide personalized therapy selection, optimizing drug-delivery systems, and exploring rational drug combinations. Emerging technologies, including nanotechnology-based delivery systems, CRISPR-mediated gene editing, and chimeric antigen receptor-T cell therapies, hold significant potential for transforming medulloblastoma treatment paradigms but require further refinement to address toxicity, off-target effects, and biomarker development. Advancing innovative, less toxic therapeutic strategies through the integration of molecular diagnostics and precision therapies is essential to improving survival outcomes and quality of life for children with medulloblastomas.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"75-90"},"PeriodicalIF":5.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12847137/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145410709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Can MicroRNAs Serve as Diagnostic Biomarkers for Glaucoma? A Systematic Review and Meta-analysis of Their Diagnostic Significance.","authors":"Kai-Yang Chen, Hoi-Chun Chan, Chi-Ming Chan","doi":"10.1007/s40291-025-00818-1","DOIUrl":"10.1007/s40291-025-00818-1","url":null,"abstract":"<p><strong>Background: </strong>Glaucoma is a leading cause of irreversible blindness worldwide. Current diagnostic methods often fail to detect disease at early stages. MicroRNAs (miRNAs), owing to their regulatory role in gene expression, have been investigated as potential biomarkers, although their diagnostic utility and clinical feasibility remain under evaluation.</p><p><strong>Objectives: </strong>The aim of this work is to systematically review and synthesize evidence on the diagnostic significance of microRNAs and related genetic markers in glaucoma and its subtypes.</p><p><strong>Methods: </strong>A systematic review and meta-analysis was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, including 16 studies with 17,300 participants. Odds ratios (ORs) and log ORs with 95% confidence intervals (CIs) were pooled using fixed-effects models. Subgroup analyses were performed by sample type, glaucoma subtype, and molecular pathway.</p><p><strong>Results: </strong>Specific miRNAs (e.g., miR-143-3p, miR-182) were significantly associated with glaucoma (OR 6.32, 95% CI 5.31-7.54, p < 0.001). Stronger correlations were observed in aqueous humor samples (OR 13.79, 95% CI 6.81-27.94, p < 0.001). Dysregulation of miRNAs was linked to increased retinal ganglion cell apoptosis and altered aqueous humor osmolality. Genetic analysis showed that common alleles in ATOH7 (OR 1.55, 95% CI 1.40-1.72) and CDKN2B (OR 1.66, 95% CI 1.55-1.78) significantly increased glaucoma risk, while miR182 variants also showed strong associations. The autotaxin (ATX)-lysophosphatidic acid (LPA) pathway was consistently implicated (OR 3.94, 95% CI 2.46-6.32).</p><p><strong>Conclusions: </strong>MiRNAs, particularly in blood samples, show promise as feasible biomarkers for early glaucoma detection, while aqueous-humor-based testing remains clinically limited owing to invasiveness. Genetic variants such as ATOH7, CDKN2B, and miR182 modestly but consistently contribute to glaucoma susceptibility. Large-scale longitudinal studies are warranted to validate these findings and translate them into routine clinical practice.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"149-168"},"PeriodicalIF":5.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145844480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dengue Fever Diagnosis: Performance Characteristics of Current Tests and Emerging Detection Technologies.","authors":"Radwa Ewaisha, Marwa Saady, Laila Khalifa, Hassan Mohamed El-Said Azzazy","doi":"10.1007/s40291-025-00822-5","DOIUrl":"10.1007/s40291-025-00822-5","url":null,"abstract":"<p><p>Dengue fever, caused by the dengue virus and transmitted primarily by Aedes mosquitoes, poses significant public health challenges across tropical and subtropical regions. With rising temperatures, changing mosquito habitats, and increasing global dengue incidence including to countries previously dengue-naive, accurate and timely diagnosis is crucial for effective disease management and outbreak control. This review explores the current state of both laboratory and point-of-care (POC) tests for dengue fever diagnosis. We discuss the performance characteristics, specifically sensitivity and specificity, of commercially available diagnostic options, highlighting their strengths and limitations. Additionally, we discuss emerging biosensor technologies designed for POC dengue diagnosis, which hold promise but are largely still in development. This overview aims to highlight the evolving landscape of dengue diagnostics and the potential impact of novel technologies.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"91-110"},"PeriodicalIF":5.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145776269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Smart Nanomedicines for Neurodegenerative Diseases: Empowering New Therapies with Molecular Imaging and Artificial Intelligence.","authors":"Jaison Jeevanandam, Grygoriy Tsenov, Michael K Danquah, Daniel Ruiz-Molena, Stergios Boussios, Saak V Ovsepian","doi":"10.1007/s40291-025-00813-6","DOIUrl":"10.1007/s40291-025-00813-6","url":null,"abstract":"<p><p>Neurodegenerative diseases (NDDs) remain among the most challenging disorders to treat, owing to their multifactorial pathology, limited drug delivery across the blood-brain barrier, and lack of effective disease-modifying therapies. Smart nanomedicines are emerging as powerful tools to overcome these challenges by enabling targeted delivery, controlled release, and enhanced bioavailability of therapeutics. In parallel, advances in molecular imaging, combined with machine learning (ML) and artificial intelligence (AI), are transforming the design, validation, and optimization of nanomedicines. This article integrates the rapidly evolving fields of nanomedicine and AI/ML-driven imaging to evaluate their synergistic potential toward NDD therapy. The capabilities of AI-aided imaging for mapping nanomedicine biodistribution, predicting therapeutic outcomes, guiding nanoparticle design, and ensuring quality control at preclinical and clinical stages in NDDs are discussed. This synergistic approach opens new avenues for precision medicine, enabling personalized and adaptive treatment strategies for Alzheimer's, Parkinson's, and other NDDs by linking smart nanocarriers with intelligent imaging analytics. Hence, this article presents a roadmap for translating AI-guided nanomedicine-integrated imaging platforms into clinically viable solutions, marking a paradigm shift in the diagnosis and treatment of NDDs.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"19-46"},"PeriodicalIF":5.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145253391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Utility of an RNA-based Gene Fusion Assay in Sarcoma for Diagnosis and Management: Experience in an Australian Laboratory.","authors":"Adel Shahnam, Catherine Mitchell, Christopher R McEvoy, Owen W J Prall, Huiling Xu, Andrew P Fellowes, David Y Choong, Christopher M Angel, Christine Khoo, Jia-Min Pang, Cameron Snell, Chris Van Vliet, Stephen J Luen, Susie Bae, Anne Hamilton, Jayesh Desai, Stephen B Fox, Jeremy Lewin","doi":"10.1007/s40291-025-00820-7","DOIUrl":"10.1007/s40291-025-00820-7","url":null,"abstract":"<p><strong>Background: </strong>Sarcoma represents a diverse group of over 70 subtypes with overlapping morphological and immunophenotypic features, often leading to diagnostic uncertainty. Gene fusions are commonly associated with specific sarcoma subtypes and can aid in diagnosis and management. RNA-based next-generation sequencing (NGS) enables sensitive detection of gene fusions, particularly in cases with limited tissue or ambiguous histopathology.</p><p><strong>Methods: </strong>We conducted a retrospective review of 124 patients with suspected sarcoma who underwent RNA-based NGS using the Illumina TruSight RNA Fusion Panel (TRFP) at a dedicated sarcoma centre between June 2020 and June 2023. The impact of fusion testing on diagnostic classification and treatment decisions was evaluated by expert pathologists and oncologists.</p><p><strong>Results: </strong>Gene fusions were detected in 75 of 124 cases (60%). Fusion results confirmed the initial diagnosis in 58 cases (47%) and altered the diagnosis in 17 cases (14%). In 14 cases (11%), findings directly influenced clinical management, including treatment de-escalation (nine cases) and initiation of targeted or alternative therapies (five cases). A definitive diagnosis was achieved in 59% of cases with limited tissue (41 of 70), 48% with uncertain tumour differentiation (25 of 52), and 43% with inconclusive or failed prior molecular testing (ten of 23), underscoring the utility of RNA-based NGS in diagnostically complex scenarios.</p><p><strong>Conclusions: </strong>RNA-based NGS fusion panels provide diagnostic and clinical utility in the evaluation of mesenchymal tumours. Their integration into routine diagnostic workflows improves diagnostic accuracy and informs personalised treatment decisions, especially in diagnostically complex or resource-limited settings.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"137-148"},"PeriodicalIF":5.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145490741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Evolving Landscape of Stem Cell Therapies for Huntington's Disease.","authors":"Marc Estarellas, Cinta Gomis, Josep M Canals","doi":"10.1007/s40291-025-00816-3","DOIUrl":"10.1007/s40291-025-00816-3","url":null,"abstract":"<p><p>Huntington's disease (HD) is a fatal, inherited neurodegenerative disorder marked by the progressive and selective loss of spiny projection neurons (SPNs), resulting in a characteristic triad of motor, cognitive, and psychiatric symptoms. Despite ongoing research, no disease-modifying treatments are available, and existing therapies are limited to symptomatic relief. Stem cell-based approaches represent a promising avenue to restore striatal circuitry by replacing lost neurons and/or delivering trophic support to preserve the remaining neural tissue.In this review, we present a critical analysis of past and current clinical trials exploring cell-based therapies for HD. Early studies using human fetal tissue were hindered by sample heterogeneity and inconsistent outcomes, ultimately limiting their clinical applicability. More recent trials have shifted focus toward mesenchymal stem cells (MSCs), which are valued for their neuroprotective secretome but are not suitable for neuronal replacement. To address these limitations, human pluripotent stem cells (hPSCs) have emerged as a renewable and scalable source for the development of advanced therapy medicinal products (ATMPs). In vitro differentiation protocols mimic key developmental signaling pathways to generate striatal-like neural progenitor cells (NPCs). We review the cellular composition of these hPSC-derived ATMPs and summarize findings from preclinical transplantation studies, including data on graft survival, neuronal maturation, synaptic integration, and functional recovery. In addition, we discuss other emerging strategies such as direct neuronal reprogramming. Finally, we examine the major challenges that remain-such as ensuring graft safety, consistency, and regulatory compliance-and highlight the importance of international collaboration to overcome these barriers and accelerate clinical translation.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"47-73"},"PeriodicalIF":5.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12847195/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145410659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Zopapogene Imadenovec: First Approval.","authors":"Arnold Lee","doi":"10.1007/s40291-025-00819-0","DOIUrl":"10.1007/s40291-025-00819-0","url":null,"abstract":"<p><p>Zopapogene imadenovec (PAPZIMEOS™; zopapogene imadenovec-drba) is a novel non-replicating adenoviral vector-based immunotherapy that stimulates an immune response against human papillomavirus (HPV) types 6 and 11. It is being developed by Precigen, Inc. for the treatment of recurrent respiratory papillomatosis, as these HPV types are causative agents for this condition. Treatment with zopapogene imadenovec resulted in complete responses in approximately half of treated patients and was associated with a papillary microenvironment that was conducive to T cells in complete responders. This article summarizes the milestones in the development of zopapogene imadenovec leading to this first approval for the treatment of adult patients with recurrent respiratory papillomatosis.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"169-171"},"PeriodicalIF":5.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145472401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dorocubicel: First Approval.","authors":"Arnold Lee","doi":"10.1007/s40291-025-00824-3","DOIUrl":"10.1007/s40291-025-00824-3","url":null,"abstract":"<p><p>Dorocubicel (Zemcelpro^®) is a cell therapy that includes UM171-expanded CD34⁺ haematopoietic stem cells derived from umbilical cord blood. It is being developed by Cordex Biologics for the treatment of haematological malignancies and non-malignant haematological disorders. In patients with haematological malignancies requiring an allogeneic haematopoietic stem cell transplantation (HSCT), transplantation with dorocubicel has been shown to result in neutrophil and platelet engraftment, as well as rapid T cell reconstitution. This article summarizes the key milestones in the development of dorocubicel leading to this first approval for the treatment of adult patients with haematological malignancies who require an allogeneic HSCT following myeloablative conditioning, for whom no other type of suitable donor cells is available.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"173-176"},"PeriodicalIF":5.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145670694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From PIK3CA Mutations to Rational PI3K Inhibition for the Treatment of Colorectal Cancer.","authors":"Ioannis A Voutsadakis","doi":"10.1007/s40291-025-00815-4","DOIUrl":"10.1007/s40291-025-00815-4","url":null,"abstract":"<p><p>Inhibitors of kinase PI3K have been in clinical development for several years but only two drugs, the alpha catalytic sub-unit specific inhibitor alpelisib and more recently inavolisib, also an inhibitor of the alpha catalytic sub-unit, have been approved for a cancer indication, in metastatic breast cancer. In colorectal cancer, despite a high prevalence of PIK3CA gene mutations, PI3K inhibitors have met with limited success, and development has mostly been halted or stagnated. Inherent resistance of colorectal cancer cells to PI3K inhibitors relate to the molecular alterations of this cancer, which include concomitant mutations and copy number alterations in other key players of the receptor tyrosine kinase pathways, including KRAS and BRAF. These have not been addressed adequately during clinical development of PI3K inhibitors. Most early trials examining PI3K inhibitors did not mandate for molecular alterations of PIK3CA as an inclusion criterion. These trials have sought to potentiate the action of other inhibitors of receptor tyrosine kinase pathways using PI3K inhibitors as a non-specific prevention against feedback resistance development. In addition, trials that included patients with PIK3CA-mutated cancers failed to consider mutations in other genes of the pathway, which may be related to primary or induced resistance. Other factors, such as the specific type of PIK3CA mutations arising in the catalytic domain, the helical domain, or other areas of the gene, which may affect the mutation functional repercussions and the inhibitor effectiveness, have not been fully taken into consideration. This review details the progress of PI3K inhibitors' development in colorectal cancer, addresses hurdles in development, and proposes areas for potential advancement.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"5-17"},"PeriodicalIF":5.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12847147/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}