Molecular Diagnosis & Therapy最新文献

{"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":"https://doi.org/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":""},"PeriodicalIF":4.4,"publicationDate":"2025-10-09","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":"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":"https://doi.org/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":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Personalized Medicine in Cystic Fibrosis: Characterization of Eight Rare CFTR Variants in Intestinal Organoids and Cellular Models.","authors":"Violeta Railean, Cláudia S Rodrigues, Ines Pankonien, Sofia S Ramalho, Iris A L Silva, Tereza Doušová, Susana Castanhinha, Pilar Azevedo, Juliana Roda, Carlos M Farinha, Margarida D Amaral","doi":"10.1007/s40291-025-00806-5","DOIUrl":"https://doi.org/10.1007/s40291-025-00806-5","url":null,"abstract":"<p><strong>Background: </strong>Despite the approval of CFTR modulator (CFTRm) drugs for specific variants, many people with cystic fibrosis with non-eligible genotypes may still benefit from these medications. Indeed, recent studies show that some rare CFTR variants can be rescued by approved CFTRm drugs.</p><p><strong>Objective: </strong>we assessed the efficacy of CFTRm drugs on eight rare CFTR variants: p.Pro5Leu, p.Pro205Ser, p.Leu206Trp, p.Arg347Pro, p.Ile507del, p.Ser945Leu, p.Met1137Arg, and p.Asp1152His.</p><p><strong>Methods: </strong>Patient-derived intestinal organoids with these variants in heterozygosity with other cystic fibrosis-causing ones were analyzed by the forskolin-induced swelling assay. Clinical data from individuals undergoing CFTRm therapy were collected both before and after treatment to evaluate clinical benefit. Furthermore, we characterized the molecular defect of those eight variants individually in cystic fibrosis bronchial epithelial cells.</p><p><strong>Results: </strong>CFTR function in intestinal organoids with genotypes p.Asp1152His/p.Phe508del, p.Asp1152His/p.Asn1303Lys, p.Pro5Leu/p.Phe508del, p.Leu206Trp/p.Phe508del, p.Ser945Leu/p.Phe508del, p.Pro205Ser/p.Tyr1092Ter, and p.Met1137Arg/c.2657+5G>A was rescued by currently available CFTRm drugs, this was not observed for organoids with genotypes p.Arg347Pro/p.Phe508del (elexacaftor/tezacaftor/ivacaftor was not tested) and p.Ile507del/p.Gln890Ter. People with cystic fibrosis who, based on our data, started CFTRm therapy showed a clinical improvement, including an increase in lung function, and a reduction in sweat chloride levels. A positive correlation was observed between forskolin-induced swelling values and change in forced expiratory volume in 1 second. This study provides evidence that the forskolin-induced swelling assay using patient-derived intestinal organoids can effectively predict the clinical outcome of CFTRm treatment. In CFBE cells, all eight variants were found to have a processing defect and variants p.Pro5Leu, p.Pro205Ser, p.Leu206Trp, p.Arg347Pro, p.Ser945Leu, and p.Met1137Arg were functionally rescued by the current available CFTRm drug. The CFTRm drug did not elicit the appearance of mature p.Ile507del-CFTR and increased, albeit not significantly, the processing efficiency of p.Asp1152His-CFTR.</p><p><strong>Conclusions: </strong>This work highlights the importance of using patient-derived intestinal organoids as a theranostic tool to predict the clinical benefit and thus increase the number of people with cystic fibrosis with access to the currently approved CFTRm therapies. While theratyping in cell lines is a valuable approach, additional testing in cystic fibrosis-derived organoids provides more reliable predictions for the individuals carrying rare CFTR variants.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145056198","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":"Inter-Assay Variability of TROP2 Immunohistochemistry in Triple-Negative Breast Cancer.","authors":"Giulia Cursano, Alberto Concardi, Mariia Ivanova, Chiara Frascarelli, Eltjona Mane, Elisa Mangione, Stefano Santaguida, Daniela Tosoni, Salvatore Pece, Antonio Marra, Carmen Criscitiello, Giuseppe Curigliano, Giuseppe Viale, Konstantinos Venetis, Elena Guerini Rocco, Nicola Fusco","doi":"10.1007/s40291-025-00814-5","DOIUrl":"https://doi.org/10.1007/s40291-025-00814-5","url":null,"abstract":"<p><strong>Background and objective: </strong>Sacituzumab govitecan, an anti-trophoblast cell surface antigen 2 (TROP2) antibody-drug conjugate, has been approved by both the US Food and Drug Administration and European Medicines Agency for patients with metastatic triple-negative breast cancer who have received two or more prior systemic therapies, including at least one of them for advanced disease. Although TROP2 evaluation is not required for patient selection, survival data from the ASCENT trial show improved response rates in patients with high TROP2 expression by immunohistochemistry. However, there is no standardized testing assay for these patients. This study evaluated the consistency of TROP2 expression analysis across different immunohistochemistry assays.</p><p><strong>Methods: </strong>Twenty-six triple-negative breast cancer samples were analyzed using three different immunohistochemistry assays on a Dako Omnis platform, according to manufacturer protocols. Specifically, ENZO-ABS380-0100 (assay A, used in ASCENT), Abcam SP295 (assay B, used in TROPiCS-02), and Santa Cruz B9-sc-376746 (assay C, used in cross-sectional studies). TROP2 expression on tumor cell membranes was quantified using the H-score, categorized as low (≤ 100), intermediate (> 101 to ≤ 200), and high (> 200). Assay agreement was evaluated using Cohen's κ and Gwet's AC2 statistics.</p><p><strong>Results: </strong>Assay A showed a broader range of TROP2 expression, with 57.7% of samples (n = 15) classified as low, 34.6% (n = 9) as intermediate, and 7.7% (n = 2) as high expressors. Assay B identified only n = 5 (19.2%) low expressors, n = 11 (42.3%) intermediate, and n = 10 (38.4%) high. While assay C identified n = 4 (15.4%) low expressors, n = 12 (46.2%) intermediate, and n = 10 (38.4%) high. Not surprisingly, assays B and C exhibited substantial agreement, with 80.8% of cases showing consistent results (κ = 0.81; p < 0.0001), indicating similar staining outcomes for TROP2 expression. The overall concordance between Assay A, B, and C was fair to moderate (AC2 = 0.35, p = 0.0067).</p><p><strong>Conclusions: </strong>Our hypothesis-generating study highlights significant variability among TROP2 assays, suggesting differences in sensitivity and specificity for triple-negative breast cancer. We demonstrate that TROP2 expression is both heterogeneous and dynamic across samples and assays, highlighting the need for methodological improvements in testing. Future research integrating computational pathology with standardized immunohistochemistry protocols and quantitative scoring systems may enhance the clinical utility of TROP2 as a biomarker in triple-negative breast cancer.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008542","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":"Gastric Cancer Treatment New Chapter: Organoid Models Leading Personalized Medicine.","authors":"Yuan Meng, LiLi Zhang, Jie Yang, Xuerui Wang, Meiying Zhu, Fanming Kong","doi":"10.1007/s40291-025-00808-3","DOIUrl":"https://doi.org/10.1007/s40291-025-00808-3","url":null,"abstract":"<p><p>Gastric cancer is a highly heterogeneous disease, with substantial variations observed among patients in clinical manifestation, histological characteristics, and drug sensitivities. Achieving precision medicine necessitates a comprehensive understanding of the molecular mechanisms underlying gastric cancer and the establishment of robust preclinical models. Organoids, cultivated from cancer cells within tumor tissues, utilizing three-dimensional tissue culture techniques, faithfully replicate the features and heterogeneity of in vivo tumors and have emerged as a promising platform. This review explores the application of gastric cancer-derived organoids (GCOs) in preclinical research and clinical translation, highlighting current challenges and outlining future prospects. Although this technology remains some distance from direct clinical application, it holds tremendous potential for clinical utilization.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144994055","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 Role of MicroRNAs in the Pathogenesis and as Biomarkers for Pediatric Epilepsy: A Systematic Review.","authors":"Fady Zakaria, Steven Amged Yousef, Janna AbdelDayem, Rawan ElGamal, Omar Y Issa, Mohamed Mansour, Harvey Bastorous, Eslam Emad, Rudayna Mahgoub","doi":"10.1007/s40291-025-00791-9","DOIUrl":"10.1007/s40291-025-00791-9","url":null,"abstract":"<p><strong>Purpose: </strong>Epilepsy is highly prevalent among children, making it one of the most common neurological diseases in the pediatric population. Its diagnosis is problematic, largely depending on clinical judgment and inaccurate investigative studies. Thus, a more objective investigation is warranted. MicroRNAs (miRNAs) are small molecules found in various body fluids and tissues that prove to have potential, as they play an important role in the pathogenesis of epilepsy. This review evaluates the use of miRNAs in the diagnosis, prediction, and prognosis of pediatric epilepsy. Furthermore, it discusses the use of miRNAs as therapeutic agents and the relationship between miRNAs and antiepileptic drugs (AEDs).</p><p><strong>Methods: </strong>From inception until 7 July 2024, a thorough search of PubMed, Europe PMC, PubMed Central, and Google Scholar was conducted.</p><p><strong>Results: </strong>Our review is based on 18 studies on pediatric patients with epilepsy according to the selection criteria. A total of 33 different miRNAs for diagnosis, 13 for prediction, and 2 for prognosis of pediatric epilepsy in a total sample size of 663, 111, and 163 pediatric patients, respectively, in addition to 20 miRNAs for the diagnosis of focal epilepsy, and a further 4 for generalized epilepsy in the same population were interpreted in our systematic review.</p><p><strong>Conclusions: </strong>These studies suggest that miRNA usage as a diagnostic, predictive, and prognostic biomarker for pediatric patients with epilepsy is promising. However, further research on that population is needed, as the number of studies is limited, with several bias concerns and heterogeneity, with the need for clinical trials to assess the use of miRNAs as drug agents. PROSPERO registration no. ID: PROSPERO 2024 CRD42024578258.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"571-589"},"PeriodicalIF":4.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12436486/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144250563","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":"Advances in Understanding Long COVID: Pathophysiological Mechanisms and the Role of Omics Technologies in Biomarker Identification.","authors":"Mônica Duarte da Silva, Thamires Santos da Silva, Claudemir Gregório Mendes, Maria Carolina Miglino Valbão, Abraham Kwame Badu-Tawiah, Lucas Fornari Laurindo, Sandra Maria Barbalho, Rosa Direito, Maria Angélica Miglino","doi":"10.1007/s40291-025-00792-8","DOIUrl":"10.1007/s40291-025-00792-8","url":null,"abstract":"<p><p>Long coronavirus disease (COVID) is a multisystem condition that affects a significant proportion of individuals following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, with persistent symptoms ranging from fatigue and cognitive dysfunction to cardiovascular disorders. It is estimated that 30-60% of infected individuals experience symptoms lasting more than 12 weeks. Despite advances in understanding acute infection, the pathophysiological mechanisms underlying long COVID remain unclear. Current hypotheses suggest that viral persistence, immune dysfunction, and metabolic alterations play central roles. Omics approaches, including metabolomics, proteomics, and lipidomics, have played a crucial role in investigating molecular changes, identifying biomarkers, and refining therapeutic strategies. This review discusses recent advances in understanding long COVID, addressing its mechanisms, risk factors, the impact of viral variants, and the role of vaccination, with an emphasis on the importance of omics technologies in elucidating this condition.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"617-636"},"PeriodicalIF":4.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12436531/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144327536","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":"Circulating Tumor DNA Profiling Reveals Genomic Evolution in Recurrent Gastric or Gastroesophageal Junction Cancer.","authors":"Ryohei Kawabata, Hiroyuki Takeda, Atsushi Ishiguro, Shinichi Nishina, Masazumi Takahashi, Shuhei Suzuki, Takahisa Suzuki, Jin Matsuyama, Yasufumi Otsuki, Yusuke Akamaru, Naoki Takegawa, Takashi Nomura, Yosuke Kito, Hiroshi Yabusaki, Yuji Negoro, Akitaka Makiyama, Masato Nakamura, Masaki Takahashi, Yu Sunakawa","doi":"10.1007/s40291-025-00807-4","DOIUrl":"https://doi.org/10.1007/s40291-025-00807-4","url":null,"abstract":"<p><strong>Background: </strong>Recurrent gastric or gastroesophageal junction cancers have poor prognoses and limited treatment options. While archival tumor tissue is commonly used for genomic profiling, it may not reflect molecular changes at recurrence.</p><p><strong>Objective: </strong>We aimed to assess the utility of a circulating tumor DNA analysis in identifying actionable genomic alterations at recurrence and compare findings with archival primary tumor profiles.</p><p><strong>Methods: </strong>This prospective multicenter observational study included 50 patients with recurrent stage II or III gastric or gastroesophageal junction adenocarcinoma who had undergone curative surgery and adjuvant chemotherapy. A circulating tumor DNA analysis was performed using the Guardant360 assay at recurrence, and results were compared with comprehensive genomic profiling from archival primary tumor tissue when available. The primary endpoint was the detection rate of actionable genomic alterations in circulating tumor DNA, defined as those with an OncoKB level ≥ 3 in any cancer type.</p><p><strong>Results: </strong>Circulating tumor DNA was detected in 78% (39/50) of patients. Actionable genomic alterations were identified in 36%, meeting the primary endpoint. The most frequent actionable genomic alterations included PIK3CA mutations (18%), ARID1A mutations (10%), ERBB2 amplification (6%), and ATM mutations (6%). Among 18 patients with paired tissue and circulating tumor DNA data, 66.7% showed changes in actionable genomic alterations between the primary tumor and recurrence. New actionable alterations, including ERBB2 amplifications and PIK3CA mutations, were identified exclusively in circulating tumor DNA at recurrence.</p><p><strong>Conclusions: </strong>A circulating tumor DNA analysis effectively captured genomic evolution at recurrence, identifying clinically relevant alterations not found in primary tumor tissue. These findings support the integration of a liquid biopsy into clinical practice to guide treatment for recurrent gastric or gastroesophageal junction cancer.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144976066","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":"Current Methods in Clinical Alzheimer's Disease Research and Diagnosis.","authors":"Eleftheria Kodosaki, Henrik Zetterberg, Amanda Heslegrave","doi":"10.1007/s40291-025-00789-3","DOIUrl":"10.1007/s40291-025-00789-3","url":null,"abstract":"<p><p>Early and accurate diagnosis of Alzheimer's disease is crucial for enabling timely intervention and improving patient outcomes. Recent advancements in molecular and imaging methodologies have significantly enhanced the detection of Alzheimer's disease at its early stages and have improved the quality of research in the field. Key molecular approaches include the identification of biomarkers such as amyloid-beta plaques and tau protein tangles, which are central to Alzheimer's disease pathology. These biomarkers can be detected through biofluid analysis or imaging methods, offering high sensitivity, however with disadvantages, which are discussed here. Despite the transition of some of these methods from research settings to clinical practice, several challenges persist, including the need for standardisation across diagnostic platforms and ensuring the accessibility of these advanced technologies within diverse healthcare systems. Additionally, the high cost and requirement for specialised expertise remain significant barriers. Here, we discuss the need to improve the effectiveness of early AD diagnosis, the ongoing research that is being conducted to refine biomarker detection, enhance imaging techniques and develop more cost-effective non-invasive diagnostic approaches. These advancements are essential to overcoming current limitations and ensuring a broader application in clinical settings.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"591-602"},"PeriodicalIF":4.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144250562","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":"Utilization of a Multi-modal Comprehensive Genomic and Immune Profiling Testing Strategy Results in a High Rate of Test Success and Detection of Clinically Relevant Biomarkers While Optimizing Tissue Usage.","authors":"Michelle F Green, Zachary D Wallen, Heidi C Ko, Kyle C Strickland, Alicia Dillard, Jeffrey M Conroy, Durga P Dash, Mary K Nesline, Paul DePietro, Shengle Zhang, Kamal S Saini, Pratheesh Sathyan, Marcia Eisenberg, Brian Caveney, Shakti Ramkissoon, Eric A Severson, Rebecca A Previs","doi":"10.1007/s40291-025-00793-7","DOIUrl":"10.1007/s40291-025-00793-7","url":null,"abstract":"<p><strong>Background: </strong>Molecular profiling is quickly becoming standard for patients with advanced cancer, with an increasing number of biomarker-directed therapies and innovative precision diagnostics available. However, with the expansion of relevant biomarkers, clinicians often face challenges obtaining optimal detection from limited tumor tissue. Here, we present biomarker detection rates from comprehensive genomic and immune profiling (CGIP) performed as a component of routine clinical care using a multi-modal testing strategy.</p><p><strong>Methods: </strong>CGIP was performed on 20,645 solid tumor specimens in a CAP/CLIA and NYS CLEP-certified reference laboratory, including DNA- and RNA-based next-generation sequencing (NGS), RNA gene expression profiling, and PD-L1 immunohistochemistry (IHC). RNA and DNA were co-extracted to optimize tissue usage. Clinical significance of detected biomarkers was classified in accordance with the joint consensus recommendations of the Association for Molecular Pathology (AMP), American Society of Clinical Oncology (ASCO), and the College of American Pathologists (CAP).</p><p><strong>Results: </strong>Adequacy of specimens for analysis with each test component varied from 99.8% (20,612) for PD-L1 IHC to 87.7% (18,113) for RNA-based NGS. DNA-based NGS had a > 96.0% success rate across all result components (short variants, copy number alterations, and genomic signatures), while RNA-based NGS and gene expression profiling were successful for 92.1% (16,689) and 90.2% (17,275) of cases, respectively. Median turnaround time from specimen receipt in the testing laboratory to report delivery was 8 days (range 1-35). Within our cohort of 15,815 cases with complete results available, 61.0% (9650) had at least one tier 1 biomarker with known clinical significance, 88.8% (14,039) had at least one tier 2 biomarker with potential clinical significance, 57.5% (9,090) had both tier 1 and 2 biomarkers, and 7.7% (1216) had no clinically significant biomarkers detected. Biomarker detection rates varied across tumor types, increasing with the addition of testing modalities.</p><p><strong>Conclusions: </strong>Utilization of a multi-modal CGIP testing strategy resulted in a high rate of test success and detection of clinically relevant biomarkers while optimizing tissue usage.</p>","PeriodicalId":49797,"journal":{"name":"Molecular Diagnosis & Therapy","volume":" ","pages":"675-688"},"PeriodicalIF":4.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12436477/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144250564","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}