Molecular Diagnosis & Therapy最新文献

{"title":"Neoantigen Targeting as a Novel Approach for Therapy-Resistant Tumors.","authors":"Masahiro Okada, Satoru Yamasaki, Go R Sato, Kanako Shimizu, Shin-Ichiro Fujii","doi":"10.1007/s40291-026-00842-9","DOIUrl":"10.1007/s40291-026-00842-9","url":null,"abstract":"<p><p>Neoantigens have emerged as central targets in the development of individualized cancer vaccines, as they are recognized by the immune system as foreign and can elicit potent anti-tumor responses. Advances in computational algorithms and machine learning have improved the accuracy of neoantigen prediction, and clinical trials have reported promising results of vaccines incorporating validated neoantigens into peptide, RNA, or dendritic cell platforms. Despite this progress, the identification of immunologically effective neoantigens remains a complex multi-step process. Current attention is directed not only to conventional missense and indel mutations but also to non-coding RNA-derived neoantigens. A critical challenge is the establishment of reliable systems to verify whether candidate neoantigens can activate cytotoxic T lymphocytes. Moreover, neoantigen expression and immune responses are influenced by tumor-intrinsic and therapeutic factors. High programmed death-ligand 1 expression is known to suppress immune recognition, while ARID1A mutations, associated with tumor progression, can enhance neoantigen expression during chemoresistance, suggesting that drug resistance may be accompanied by new immunogenicity. This work provides an overview of current methodologies for neoantigen identification, advances in prediction and validation strategies, and the dynamic interplay between tumor-intrinsic and immune-related factors that regulate neoantigen expression. We also highlight recent clinical insights as well as novel analytical approaches and discuss challenges and future directions in this rapidly evolving field, emphasizing the potential of neoantigen-based therapies to transform cancer immunotherapy.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"495-514"},"PeriodicalIF":5.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13172014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147582814","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":"The Evolving Role of Genomic Technologies in Multiple Myeloma: Implications for Diagnosis, Risk Stratification and Resistance.","authors":"Klára Baďurová, Veronika Kapustová, Jana Kotulová, Vítězslav Brinsa, Lenka Piherová, Václav Janoušek, Michal Pohludka, Michal Richtář, Tomáš Jelínek, Roman Hájek, Zuzana Chyra, Tereza Ševčíková","doi":"10.1007/s40291-026-00836-7","DOIUrl":"10.1007/s40291-026-00836-7","url":null,"abstract":"<p><p>Plasma cell disorders range from indolent precursors to aggressive malignancies, with multiple myeloma as the most common malignant form. Multiple myeloma biology is highly complex and driven by genomic heterogeneity. Although recent genomic advances offer increasingly precise treatment strategies, routinely used conventional diagnostic methods sometimes fail to reflect the evolution of up-to-date multiple myeloma risk stratification models, and the implementation of genomic discoveries into clinical guidelines is hindered. We reviewed the current state and emerging roles of genomic diagnostics in multiple myeloma and related conditions, emphasizing the clinical utility. We summarized clinical presentation and diagnostic criteria, mapped the mutational landscape across disease stages, and tracked the evolution of risk stratification from clinical staging to integrated genomic models. We also highlighted recent recommendations that incorporate a quantitative assessment of cytogenetic abnormalities and tumor suppressor gene mutations. Further, we compared routinely used and state-of-the-art technologies including fluorescence in situ hybridization, targeted gene panels, whole-exome and whole-genome sequencing, long-read platforms, optical genome mapping, and analyses of circulating tumor DNA, focusing on their strengths, limitations, and complementary roles in the baseline work-up, longitudinal monitoring, and detection of resistance. Last, we discussed practical barriers to implementation and proposed a framework for proactive integration of novel approaches into clinics. In summary, comprehensive genomic profiling is becoming central to modern multiple myeloma diagnostics and a key step for precise and personalized medicine that will, if integrated into routine care, enable a more precise risk assessment, earlier detection of relapse, and improved therapy selection.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"475-494"},"PeriodicalIF":5.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13171931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147576342","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":"Exosomal Cargo-Derived Mediators of Ovarian Cancer Chemoresistance.","authors":"Szymon Rutecki, Krzysztof Książek, Justyna Mikuła-Pietrasik","doi":"10.1007/s40291-026-00844-7","DOIUrl":"10.1007/s40291-026-00844-7","url":null,"abstract":"<p><p>Exosomes are small extracellular vesicles secreted by various cells. They play a vital role in intercellular communication due to their diverse molecular cargo. Recent advancements in biomedical research have enabled a more detailed characterization of exosomes and their significant role in cancer biology, particularly in understanding mechanisms that contribute to chemoresistance. This review focuses on the current understanding of exosomes in ovarian cancer, one of the deadliest gynecological malignancies, known for its high recurrence and treatment failure rates. Chemoresistance in ovarian cancer stems from several factors, including altered drug efflux, enhanced DNA repair mechanisms, changes in the tumor microenvironment, and modifications in signaling pathways. Emerging evidence suggests that exosomes facilitate these processes by transferring regulatory molecules such as proteins, microRNAs (miRNAs), and circular RNAs (circRNAs) between cells, which in turn modulate drug response and tumor progression. For instance, exosomal proteins such as DNA methyltransferase 1 (DNMT1) and circular forkhead box P1 (circFoxp1), along with miRNAs like miR-21-3p, miR-1246, and miR-6836, have been associated with promoting resistance to platinum- and taxane-based chemotherapies. Conversely, some exosomal miRNAs, including miR-30a-5p, may enhance drug sensitivity. Furthermore, circRNAs transported by exosomes, such as hsa_circ_0010467, circ-PIP5K1A, and circ_0025033, play a role in regulating key oncogenic pathways associated with chemoresistance. Overall, these findings highlight the multifaceted role of exosomes in ovarian cancer biology and underscore their potential as both biomarkers and therapeutic targets. A deeper understanding of how exosomes mediate molecular mechanisms may lead to novel strategies for overcoming chemoresistance and improving treatment outcomes for ovarian cancer patients.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"463-474"},"PeriodicalIF":5.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147576301","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":"RNA Aptamers and Epitranscriptomics: Charting Unexplored Territories in RNA Biology.","authors":"Mehran Khorshid, Ehsan Pashay Ahi","doi":"10.1007/s40291-026-00841-w","DOIUrl":"10.1007/s40291-026-00841-w","url":null,"abstract":"<p><p>The fields of RNA aptamers and epitranscriptomics have each emerged as powerful dimensions of RNA biology, yet their conceptual and mechanistic overlap remains largely unexplored. RNA aptamers as in vitro-selected single-stranded RNA oligonucleotides selected through in vitro evolution (Systematic Evolution of Ligands by Exponential Enrichment [SELEX]) and related methods are well known for their ability to fold into precise three-dimensional structures and bind specific targets with high affinity. These aptamers have been widely used in diagnostics, therapeutics, and molecular sensing. In parallel, the dynamic landscape of epitranscriptomic modifications, such as N⁶-methyladenosine (m⁶A), pseudouridine (Ψ), and 5-methylcytosine (m⁵C), has been recognized as a critical regulator of RNA structure, stability, and function. In this perspective article, we chart unexplored territories at the interface of these two mechanisms, focusing on how RNA modifications may influence aptamer folding or binding, and how aptamers could, in turn, be harnessed to detect or modulate the epitranscriptomic state. We also highlight opportunities for cross-disciplinary integration in synthetic biology, post-transcriptional regulation, and RNA-based therapeutics. While the direct regulatory connections between these domains remain to be fully elucidated, we propose their potential convergence as a fertile ground for innovation. The primary aim of this article is to stimulate discussion within and between these research communities and to attract attention toward a promising frontier for future investigations.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"383-402"},"PeriodicalIF":5.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13171942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147469847","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":"Pre-analytical Best Practices for RNA Sequencing from Small Biopsies and Cytologic Specimens.","authors":"Gloria Hopkins Sura, Kelly B Engel, Sarah R Greytak, Sandra M Gaston, Kelsey Dillehay McKillip, Abhilasha Rao, Ping Guan, W Fraser Symmans, Rachael Clark, Maria Arcila, Sayak Ghatak, Karol Bomsztyk, Lokesh Agrawal","doi":"10.1007/s40291-026-00837-6","DOIUrl":"10.1007/s40291-026-00837-6","url":null,"abstract":"<p><p>RNA sequencing is becoming increasingly common in precision oncology, in both clinical and research settings, for transcriptome profiling, gene-fusion detection, and biomarker discovery. RNA-sequencing analysis of specimens obtained via minimally invasive procedures such as small biopsy, fine needle aspiration, and exfoliation offers a powerful method for analyzing gene expression patterns and detecting RNA-level changes associated with cancers that are either difficult to collect or require longitudinal sampling. However, pre-analytical factors (e.g., details of specimen collection, processing, and storage workflow) influence not only RNA-sequencing success rates but also the quality and accuracy of sequencing results, which may affect patient care and research progress. Minimally invasive specimens are associated with a unique set of pre-analytical challenges owing to their small size, limited RNA yield, and distinct workflows. To address the need for evidence-based guidance, this review by a working group of National Cancer Institute grantees and intramural and extramural researchers identifies pre-analytical best practices for minimally invasive specimens destined for RNA-sequencing analysis, based on the available literature and their collective experience. Strategies for assessing specimen adequacy and RNA quality, maximizing tumor content, and minimizing specimen loss and RNA degradation due to pre-analytical handling are specified for small tissue and cytology specimens. By integrating current evidence and institutional insights, this review provides a practical framework for enhancing RNA-sequencing reliability and reproducibility in both clinical and research workflows.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"441-461"},"PeriodicalIF":5.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13171677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147460703","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":"Etuvetidigene Autotemcel: First Approval.","authors":"Hannah A Blair","doi":"10.1007/s40291-026-00843-8","DOIUrl":"10.1007/s40291-026-00843-8","url":null,"abstract":"<p><p>Etuvetidigene autotemcel (WASKYRA^™) is an autologous haematopoietic stem cell (HSC)-based gene therapy being developed by Fondazione Telethon for the treatment of Wiskott-Aldrich syndrome (WAS). In December 2025, etuvetidigene autotemcel was approved in the USA for the treatment of paediatric patients aged 6 months and older and adults with WAS who have a mutation in the WAS gene for whom HSC transplantation (HSCT) is appropriate and no suitable human leukocyte antigen (HLA)-matched related stem cell donor is available. Etuvetidigene autotemcel was approved in the EU for the same indication in January 2026. This article summarizes the milestones in the development of etuvetidigene autotemcel leading to this first approval for the treatment of WAS.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"539-543"},"PeriodicalIF":5.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147516209","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":"Beyond Binary FISH Results: Targeted NGS Provides Deeper Characterization of MYC and Broader Genomic Alterations in DLBCL.","authors":"Mariana Bastos-Oreiro, Sara Fernández de Córdoba-Oñate, Ismael de la Iglesia-San Sebastián, Francisco Díaz-Crespo, María Chicano Lavilla, Juan Carlos Triviño, Raquel Fernández González, Miguel López-Esteban, Marina Gómez-Llobel, Paula Fernández Caldas, Pablo Silva, Javier Menárguez, Ramón García Sanz, Ismael Buño, Carolina Martínez-Laperche","doi":"10.1007/s40291-026-00846-5","DOIUrl":"10.1007/s40291-026-00846-5","url":null,"abstract":"<p><strong>Introduction: </strong>Rearrangements involving MYC, BCL2, and BCL6 are central to the genetic classification and risk stratification of diffuse large B cell lymphoma (DLBCL). In routine practice, these alterations are primarily assessed by fluorescence in situ hybridization (FISH), which provides limited diagnostic information and lacks information on partner genes, breakpoint architecture, or clonal complexity.</p><p><strong>Methods: </strong>We investigated whether targeted next-generation sequencing (NGS) refines the interpretation of gene rearrangements in aggressive B cell lymphomas and alters their diagnostic classification. Tumor samples from 48 patients were analyzed using FISH, immunohistochemistry, and a custom hybrid-capture NGS panel enabling simultaneous detection of structural variants, copy number alterations, and somatic mutations.</p><p><strong>Results: </strong>Targeted NGS identified 59 fusion events in 37 patients, including 26 MYC rearrangements (MYC-Rs). A substantial proportion (58%) involved non-immunoglobulin partners, many of them previously unreported. NGS resolved inconclusive or discordant FISH results, uncovered cryptic rearrangements, and revealed genomic complexity. In several cases, these findings refined genetic classification, including the identification of additional double- and triple-hit lymphomas.</p><p><strong>Conclusions: </strong>These results demonstrate that a FISH-based assessment of MYC-, BCL2-, and BCL6-Rs is insufficient to capture the biological and diagnostic complexity of DLBCL. Targeted NGS provides structural and functional context that improves interpretation of rearrangements and supports a more refined genetic classification in routine practice.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"529-538"},"PeriodicalIF":5.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147677986","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":"Colorectal Cancer: A Landscape of New Potential Radiopharmaceuticals.","authors":"Veronica Serena Cabitza, Pier Cesare Capponi, Irene Brusa, Fabrizio Vincenzi, Silvia Pasquini, Katia Varani, Luca Urso, Licia Uccelli","doi":"10.1007/s40291-026-00839-4","DOIUrl":"10.1007/s40291-026-00839-4","url":null,"abstract":"<p><p>In recent years, advancements in imaging techniques have contributed to a gradual yet promising reduction in colorectal cancer-related mortality. Among these, positron emission tomography (PET), particularly in combination with computed tomography using 2-deoxy-2-[fluorine-18]fluoro-D-glucose ([¹⁸F]FDG), has emerged as a valuable non-invasive diagnostic tool. However, the application of [¹⁸F]FDG-PET in colorectal cancer remains limited because of the radiotracer's pharmacokinetics and metabolic characteristics. As a result, [¹⁸F]FDG-PET is not routinely recommended for the initial diagnosis or staging of colorectal cancer but is primarily used for assessing treatment response and disease surveillance. Additionally, colorectal cancer imaging with [¹⁸F]FDG presents challenges related to false-positive results caused by radiotracer uptake in non-malignant conditions such as inflammatory bowel disease, polyps, Crohn's disease, and colitis. This inability to reliably distinguish between benign and malignant lesions remains a significant limitation in colorectal cancer imaging. To overcome these challenges, ongoing research is focused on the development of novel radiotracers capable of improving the specificity and accuracy of PET imaging in colorectal cancer. New radiolabeled probes are being investigated, including natural molecules, inflammatory markers, and target-specific immune elements, labeled with [¹⁸F], [⁶⁸Ga], [¹¹C], and [⁶⁴Cu], which have shown potential in preclinical studies. Among emerging radiopharmaceuticals for colorectal cancer, only [⁶⁸Ga]Ga-HNI01 and [⁶⁸Ga]Ga-FAPI-04 have advanced to preliminary clinical evaluation phases. Despite promising initial diagnostic performance, these investigations remain limited in scale and scope, necessitating further rigorous, large-scale clinical trials to validate efficacy and safety. All these advancements could significantly enhance colorectal cancer detection and characterization, leading to earlier diagnoses and better patient outcomes.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"403-426"},"PeriodicalIF":5.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13171661/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147437313","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":"Cytokines at the Crossroads of Mitochondrial Dysfunction and Inflammation in Colorectal Cancer: Implications for Postoperative Complications.","authors":"Klara Vokacova, Natalie Danesova, Ladislav Sojka, Veronika Vymetalkova","doi":"10.1007/s40291-026-00838-5","DOIUrl":"10.1007/s40291-026-00838-5","url":null,"abstract":"<p><p>Colorectal cancer (CRC) remains one of the leading causes of cancer-related morbidity and mortality worldwide, with surgery representing the cornerstone of curative treatment. Although surgical techniques and perioperative care have improved markedly, postoperative complications (POCs) still significantly affect early morbidity, prolong recovery and negatively influence long-term outcomes. These challenges have led to growing efforts to identify biological markers that could help predict adverse events and improve risk stratification. Inflammatory activation and mitochondrial dysfunction have emerged as interconnected contributors to postoperative vulnerability, and their measurable mediators represent attractive candidates for biomarker development. Cytokines, as central regulators of immune signalling, together with mitochondrial-derived danger signals (mtDAMPs) released during surgical trauma and ischemia-reperfusion injury, may enable earlier identification of patients at risk of POCs. In this review, we summarize current evidence linking key cytokines, including interleukin (IL)-6, tumour necrosis factor (TNF)-α, IL-1β and IL-10, to postoperative outcomes after CRC surgery and discuss mechanistic pathways through which cytokine signalling can modulate mitochondrial function, reactive oxygen species production and tissue integrity. We also highlight the translational potential of mitochondrial biomarkers such as circulating mitochondrial DNA, while acknowledging that CRC-specific clinical evidence remains limited and methodologically heterogeneous. Taken together, a deeper understanding of these interconnections, supported by standardized longitudinal perioperative profiling, could ultimately improve complication prediction and support more personalized strategies for POCs prevention, early detection and optimized recovery following CRC surgery.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"427-440"},"PeriodicalIF":5.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147379295","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":"Comment on: \"Personalized Medicine in Cystic Fibrosis: Characterization of Eight Rare CFTR Variants in Intestinal Organoids and Cellular Models\".","authors":"DuJiang Yang, GuoYou Wang","doi":"10.1007/s40291-025-00827-0","DOIUrl":"10.1007/s40291-025-00827-0","url":null,"abstract":"","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"377-378"},"PeriodicalIF":5.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146054672","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}