Molecular Diagnosis & Therapy最新文献

{"title":"Emerging Biohybrids of Aptamer-Based Nano-Biosensing Technologies for Effective Early Cancer Detection.","authors":"Thimmaiah Bargavi Ram, Saravanan Krishnan, Jaison Jeevanandam, Michael K Danquah, Sabu Thomas","doi":"10.1007/s40291-024-00717-x","DOIUrl":"10.1007/s40291-024-00717-x","url":null,"abstract":"<p><p>Cancer is a leading global cause of mortality, which underscores the imperative of early detection for improved patient outcomes. Biorecognition molecules, especially aptamers, have emerged as highly effective tools for early and accurate cancer cell identification. Aptamers, with superior versatility in synthesis and modification, offer enhanced binding specificity and stability compared with conventional antibodies. Hence, this article reviews diagnostic strategies employing aptamer-based biohybrid nano-biosensing technologies, focusing on their utility in detecting cancer biomarkers and abnormal cells. Recent developments include the synthesis of nano-aptamers using diverse nanomaterials, such as metallic nanoparticles, metal oxide nanoparticles, carbon-derived substances, and biohybrid nanostructures. The integration of these nanomaterials with aptamers significantly enhances sensitivity and specificity, promising innovative and efficient approaches for cancer diagnosis. This convergence of nanotechnology with aptamer research holds the potential to revolutionize cancer treatment through rapid, accurate, and non-invasive diagnostic methods.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"425-453"},"PeriodicalIF":4.1,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141075891","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":"Single-Domain Antibody-Gold Nanoparticle Bioconjugates as Immunosensors for the Detection of Hantaviruses","authors":"Erika A. Bastos-Soares, Michelle Suelen da Silva Morais, Maribel Funes-Huacca, Rosa Maria O. Sousa, Nairo Brilhante-Da-Silva, Sibele Andrade Roberto, Nidiane Dantas R. Prado, Claudia N. Duarte dos Santos, Anna C. M. Marinho, Andreimar M. Soares, Rodrigo G. Stabeli, Soraya dos Santos Pereira, Carla Freire C. Fernandes","doi":"10.1007/s40291-024-00713-1","DOIUrl":"https://doi.org/10.1007/s40291-024-00713-1","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Introduction</h3><p>Hantavirus, a zoonotic pathogen, causes severe syndromes like hemorrhagic fever with renal syndrome (HFRS), sometimes fatal in humans. Considering the importance of detecting the hantavirus antigen, the construction of an immunosensor is essential. The structural and functional characteristics of camelid nanobodies (VHHs) encourage their application in the areas of nanobiotechnology, therapeutics, diagnostics, and basic research. Therefore, this study aimed to standardize stable bioconjugates using gold nanoparticles (AuNPs) and VHHs, in order to develop immunobiosensors for the diagnosis of hantavirus infection.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Immobilized metal affinity chromatography (IMAC) was performed to obtain purified recombinant anti-hantavirus nucleocapsid nanobodies (anti-prNΔ₈₅ VHH), while AuNPs were synthesized for bioconjugation. UV-visible spectrophotometry and transmission electron microscopy (TEM) analysis were employed to characterize AuNPs.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>The bioconjugation stability parameters (VHH-AuNPs), analyzed by spectrophotometry, showed that the ideal pH value and VHH concentration were obtained at 7.4 and 50 μg/mL, respectively, after addition of 1 M NaCl, which induces AuNP aggregation. TEM performed before and after bioconjugation showed uniform, homogeneous, well-dispersed, and spherical AuNPs with an average diameter of ~ 14 ± 0.57 nm. Furthermore, high-resolution images revealed a thin white halo on the surface of the AuNPs, indicating the coating of the AuNPs with protein. A biosensor simulation test (dot blot-like [DB-like]) was performed in stationary phase to verify the binding and detection limits of the recombinant nucleocapsid protein from the Araucária hantavirus strain (prN∆₈₅).</p><h3 data-test=\"abstract-sub-heading\">Discussion</h3><p>Using AuNPs/VHH bioconjugates, a specific interaction was detected between 5 and 10 min of reaction in a dose-dependent manner. It was observed that this test was sensitive enough to detect prNΔ₈₅ at concentrations up to 25 ng/μL. Considering that nanostructured biological systems such as antibodies conjugated with AuNPs are useful tools for the development of chemical and biological sensors, the stability of the bioconjugate indicates proficiency in detecting antigens. The experimental results obtained will be used in a future immunospot assay or lateral flow immunochromatography analysis for hantavirus detection.</p><h3 data-test=\"abstract-sub-heading\">Graphical Abstract</h3>\u0000","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":"34 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141148064","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":"Lutetium-177 Labelled Anti-PSMA Monoclonal Antibody (Lu-TLX591) Therapy for Metastatic Prostate Cancer: Treatment Toxicity and Outcomes.","authors":"Hanh Nguyen, Kathryn Hird, Joe Cardaci, Steven Smith, Nat P Lenzo","doi":"10.1007/s40291-024-00699-w","DOIUrl":"10.1007/s40291-024-00699-w","url":null,"abstract":"<p><strong>Introduction: </strong>Whilst prostate cancer is the fourth most common cancer globally, effective therapies for patients with advanced disease are lacking. In recent years, interest in using theranostic agents to treat castrate-resistant prostate cancer (CRPC) and metastatic prostate cancer has emerged. Lu-TLX591 monoclonal antibody is a potential agent of significance; however, to date, reports on its toxicity and efficacy have been limited to small clinical trials in heavily pretreated patients. This retrospective study describes the real-world toxicity and efficacy profile of Lu-TLX591.</p><p><strong>Methods: </strong>Eighteen patients received Lu-TLX591 at two private oncology centres in Australia. Patients were eligible if they had CRPC or metastatic prostate cancer and prostate-specific membrane antigen (PSMA)-avid disease confirmed by PSMA-positron emission tomography (PET). Patients received two cycles of Lu-TLX591 monoclonal antibody (177 Lu-DOTA-rosopatamab) each dosed from 1.01-2.85 GBq, 14 days apart. Patient side effects, blood test results and radiology reports were recorded on the patient's electronic medical record (eMR).</p><p><strong>Results: </strong>Prominent side effects included fatigue (55.6%), anorexia (16.7%), nausea (11.1%), and transfusion reactions (11.1%). All-grade haematological toxicities included lymphopenia (61.1%), anaemia (22.2%), leukopenia (27.8%), neutropenia (27.8%), and thrombocytopenia (27.8%). Grade 4 toxicity included lymphopenia (6.7%) and thrombocytopenia (6.7%). Patients' prostate-specific antigen (PSA) responses were as follows; ≥ 30% PSA decline (27.8%), ≥ 50% PSA decline (11.4%) and any PSA decline (38.9%). Follow-up radiology revealed 54.5% stable disease, 45.4% disease progression and 9.1% disease regression.</p><p><strong>Conclusion: </strong>Lu-TLX591 was safely administered at acceptable toxicity and its efficacy reflects previous clinical trials. Larger studies are required and are underway (NCT04786847; NCT05146973; NCT04876651) to determine Lu-TLX591 effectiveness amongst different prostate cancer populations and compare its efficacy against peptide-based radiopharmaceutical agents.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"291-299"},"PeriodicalIF":4.1,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11068829/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140040725","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":"In vivo LNP-CRISPR Approaches for the Treatment of Hemophilia.","authors":"Jeong Hyeon Lee, Jeong Pil Han","doi":"10.1007/s40291-024-00705-1","DOIUrl":"10.1007/s40291-024-00705-1","url":null,"abstract":"<p><p>Hemophilia is a genetic disorder that is caused by mutations in coagulation factor VIII (hemophilia A) or IX (hemophilia B) genes resulting in blood clotting disorders. Despite advances in therapies, such as recombinant proteins and products with extended half-lives, the treatment of hemophilia still faces two major limitations: the short duration of therapeutic effect and production of neutralizing antibodies against clotting factors (inhibitor). To overcome these limitations, new hemophilia treatment strategies have been established such as gene therapy, bispecific antibody, and rebalancing therapy. Although these strategies have shown promising results, it is difficult to achieve a permanent therapeutic effect. Advances in the clustered regularly interspaced short palindromic repeat (CRISPR) technology have allowed sustainable treatment by correcting mutated genes. Since genome editing generates irreversible changes in host genome, safety must be ensured by delivering target organs. Therefore, the delivery tool of the CRISPR system is crucial for safe, accurate, and efficient genome editing. Recently, non-viral vector lipid nanoparticles (LNPs) have emerged as safer tools for delivering CRISPR systems than other viral vectors. Several previous hemophilia pre-clinical studies using LNP-CRISPR showed that sufficient and sustainable therapeutic effects, which means that LNP-CRISPR-mediated genome-editing therapy can be a valid option for the treatment of hemophilia. In this paper, we summarize the latest advancements in the successful treatment of hemophilia and the potential of CRISPR-mediated genome-editing therapy using LNPs.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"239-248"},"PeriodicalIF":4.1,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11068834/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140307530","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":"Identification of Plasmatic MicroRNA-206 as New Predictor of Early Recurrence of Atrial Fibrillation After Catheter Ablation Using Next-generation Sequencing.","authors":"Filip Šustr, Táňa Macháčková, Martin Pešl, Jana Svačinova, Karolína Trachtová, Zdeněk Stárek, Bohuslav Kianička, Ondřej Slabý, Jan Novák","doi":"10.1007/s40291-024-00698-x","DOIUrl":"10.1007/s40291-024-00698-x","url":null,"abstract":"<p><strong>Background: </strong>Catheter ablation (CA) of atrial fibrillation (AF) is indicated in patients with recurrent and symptomatic AF episodes. Despite the strict inclusion/exclusion criteria, AF recurrence after CA remains high. Identification of a novel biomarker that would predict AF recurrence would help to stratify the patients. The aim of the study was to seek novel biomarkers among the plasmatic microRNAs (miRNAs, miRs).</p><p><strong>Methods: </strong>A prospective monocentric study was conducted. A total of 49 consecutive AF patients indicated for CA were included. Blood sampling was performed prior to CA. RNA was isolated from plasma using commercial kits. In the exploration phase, small RNA sequencing was performed in ten AF patients (five with and five without AF recurrence) using Illumina instrument. In the validation phase, levels of selected miRNAs were determined using quantitative reverse transcription polymerase chain reaction (qRT-PCR) in all participants.</p><p><strong>Results: </strong>Altogether, 22 miRNAs were identified as altered between the groups by next-generation sequencing (using the DESeq2 algorithm). Using qRT-PCR, levels of the five most altered miRNAs (miR-190b/206/326/505-5p/1296-5p) were verified in the whole cohort. Plasma levels of hsa-miR-206 were significantly higher in patients with early (within 6 months) AF recurrence and showed an increase of risk recurrence,2.65 times by every increase in its level by 1 unit in the binary logistic regression.</p><p><strong>Conclusion: </strong>We have identified a set of 22 plasmatic miRNAs that differ between the patients with and without AF recurrence after CA and confirmed hsa-miR-206 as a novel miRNA associated with early AF recurrence. Results shall be verified in a larger independent cohort.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"301-310"},"PeriodicalIF":4.1,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11068688/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140066129","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":"Unwinding Helicase MCM Functionality for Diagnosis and Therapeutics of Replication Abnormalities Associated with Cancer: A Review.","authors":"Arathi Radhakrishnan, Ritwik Gangopadhyay, Chandresh Sharma, Raj Kishor Kapardar, Nilesh Kumar Sharma, Rajpal Srivastav","doi":"10.1007/s40291-024-00701-5","DOIUrl":"10.1007/s40291-024-00701-5","url":null,"abstract":"<p><p>The minichromosome maintenance (MCM) protein is a component of an active helicase that is essential for the initiation of DNA replication. Dysregulation of MCM functions contribute to abnormal cell proliferation and genomic instability. The interactions of MCM with cellular factors, including Cdc45 and GINS, determine the formation of active helicase and functioning of helicase. The functioning of MCM determines the fate of DNA replication and, thus, genomic integrity. This complex is upregulated in precancerous cells and can act as an important tool for diagnostic applications. The MCM protein complex can be an important broad-spectrum therapeutic target in various cancers. Investigations have supported the potential and applications of MCM in cancer diagnosis and its therapeutics. In this article, we discuss the physiological roles of MCM and its associated factors in DNA replication and cancer pathogenesis.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"249-264"},"PeriodicalIF":4.1,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140295124","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":"Advances in Radioligand Theranostics in Oncology.","authors":"Ismaheel O Lawal, Sofiullah O Abubakar, Honest Ndlovu, Kgomotso M G Mokoala, Stuart S More, Mike M Sathekge","doi":"10.1007/s40291-024-00702-4","DOIUrl":"10.1007/s40291-024-00702-4","url":null,"abstract":"<p><p>Theranostics with radioligands (radiotheranostics) has played a pivotal role in oncology. Radiotheranostics explores the molecular targets expressed on tumor cells to target them for imaging and therapy. In this way, radiotheranostics entails non-invasive demonstration of the in vivo expression of a molecular target of interest through imaging followed by the administration of therapeutic radioligand targeting the tumor-expressed molecular target. Therefore, radiotheranostics ensures that only patients with a high likelihood of response are treated with a particular radiotheranostic agent, ensuring the delivery of personalized care to cancer patients. Within the last decades, a couple of radiotheranostics agents, including Lutetium-177 DOTATATE (¹⁷⁷Lu-DOTATATE) and Lutetium-177 prostate-specific membrane antigen (¹⁷⁷Lu-PSMA), were shown to prolong the survival of cancer patients compared to the current standard of care leading to the regulatory approval of these agents for routine use in oncology care. This recent string of successful approvals has broadened the interest in the development of different radiotheranostic agents and their investigation for clinical translation. In this work, we present an updated appraisal of the literature, reviewing the recent advances in the use of established radiotheranostic agents such as radioiodine for differentiated thyroid carcinoma and Iodine-131-labeled meta-iodobenzylguanidine therapy of tumors of the sympathoadrenal axis as well as the recently approved ¹⁷⁷Lu-DOTATATE and ¹⁷⁷Lu-PSMA for differentiated neuroendocrine tumors and advanced prostate cancer, respectively. We also discuss the radiotheranostic agents that have been comprehensively characterized in preclinical studies and have shown some clinical evidence supporting their safety and efficacy, especially those targeting fibroblast activation protein (FAP) and chemokine receptor 4 (CXCR4) and those still being investigated in preclinical studies such as those targeting poly (ADP-ribose) polymerase (PARP) and epidermal growth factor receptor 2.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"265-289"},"PeriodicalIF":4.1,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140330271","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":"Inflammatory Gene Panel Guiding the Study of Genetics in Inflammatory Bowel Disease","authors":"Ryan Xin","doi":"10.1007/s40291-024-00709-x","DOIUrl":"https://doi.org/10.1007/s40291-024-00709-x","url":null,"abstract":"<p>Inflammatory bowel disease (IBD) is a complex disease that develops through a sequence of molecular events that are still poorly defined. This process is driven by a multitude of context-dependent genes that play different roles based on their environment. The complexity and multi-faceted nature of these genes make it difficult to study the genetic basis of IBD. The goal of this article is to review the key genes in the pathophysiology of IBD and highlight new technology that can be used in further research. This paper examines Nanostring RNA probe technology, which uses tissue analyzed without the use of enzymes, transcription, or amplification. Nanostring offers several panels of genes to test, including an inflammation panel of 234 genes. This article analyzes this panel and reviews the literature for each gene’s effect in IBD for use as a framework to review the pathophysiology of the disease. The panel was narrowed to 26 genes with significant evidence of mechanistic potential in IBD, which were then categorized into specific areas of pathogenesis. These include gut barrier breakdown, inappropriate recognition of commensal bacteria, immune cell activation, proinflammatory cytokine release, and subsequent impairment of the anti-inflammatory response. The eventual goal of this paper is the creation of a customized panel of IBD genes that can be used to better understand the genetic mechanism of IBD and aid in the development of future therapies in IBD.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":"1 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140623625","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":"Lifileucel: First Approval","authors":"Susan J. Keam","doi":"10.1007/s40291-024-00708-y","DOIUrl":"https://doi.org/10.1007/s40291-024-00708-y","url":null,"abstract":"<p>Lifileucel (AMTAGVI™), a one-time autologous T cell therapy derived and expanded from tumour-infiltrating lymphocytes (TIL) from a patient’s own tumour, is being developed by Iovance Biotherapeutics, Inc. for the treatment of cancer. Lifileucel was granted accelerated approval based on objective response rate (ORR) in February 2024 in the USA for use in adult patients with unresectable or metastatic melanoma previously treated with a PD-1 blocking antibody, and if <i>BRAF</i> V600 mutation positive, a BRAF inhibitor with or without a MEK inhibitor. This article summarizes the milestones in the development of lifileucel leading to this first approval for the treatment of patients with unresectable or metastatic melanoma who have progressed on or after prior anti-PD-1/L1 therapy and targeted therapy.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":"41 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140597556","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":"Estimating the Prognostic Value of the NTRK Fusion Biomarker for Comparative Effectiveness Research in The Netherlands","authors":"Irene Santi, Heleen Vellekoop, Matthijs M Versteegh, Simone A Huygens, Winand N. M. Dinjens, Maureen Rutten-van Mölken","doi":"10.1007/s40291-024-00704-2","DOIUrl":"https://doi.org/10.1007/s40291-024-00704-2","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Objectives</h3><p>We evaluated the prognostic value of the neurotrophic tyrosine receptor kinase (<i>NTRK</i>) gene fusions by comparing the survival of patients with <i>NTRK+ </i>tumours with patients without <i>NTRK+</i> tumours.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>We used genomic and clinical registry data from the Center for Personalized Cancer Treatment (CPCT-02) study containing a cohort of cancer patients who were treated in Dutch clinical practice between 2012 and 2020. We performed a propensity score matching analysis, where <i>NTRK+</i> patients were matched to <i>NTRK−</i> patients in a 1:4 ratio. We subsequently analysed the survival of the matched sample of <i>NTRK+</i> and <i>NTRK−</i> patients using the Kaplan–Meier method and Cox regression, and performed an analysis of credibility to evaluate the plausibility of our result.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Among 3556 patients from the CPCT-02 study with known tumour location, 24 <i>NTRK</i>+ patients were identified. <i>NTRK+</i> patients were distributed across nine different tumour types: bone/soft tissue, breast, colorectal, head and neck, lung, pancreas, prostate, skin and urinary tract. <i>NTRK</i> fusions involving the <i>NTRK3</i> gene (46%) and <i>NTRK1</i> gene (33%) were most common. The survival analysis rendered a hazard ratio (HR) of 1.44 (95% CI 0.81–2.55) for <i>NTRK+</i> patients. Using the point estimates of three prior studies on the prognostic value of <i>NTRK</i> fusions, our finding that the HR is &gt; 1 was deemed plausible.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p><i>NTRK+</i> patients may have an increased risk of death compared with <i>NTRK−</i> patients. When using historic control data to assess the comparative effectiveness of TRK inhibitors, the prognostic value of the <i>NTRK</i> fusion biomarker should therefore be accounted for.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":"48 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140597553","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}