Current Issues in Molecular Biology最新文献

{"title":"Redox-Regulated Mitophagy and Lysosomal Dysfunction as a Convergent Mechanism in Female Infertility: Molecular Insights and Therapeutic Perspectives.","authors":"Charalampos Voros, Fotios Chatzinikolaou, Georgios Papadimas, Athanasios Karpouzos, Ioannis Papapanagiotou, Aristotelis-Marios Koulakmanidis, Diamantis Athanasiou, Kyriakos Bananis, Antonia Athanasiou, Aikaterini Athanasiou, Charalampos Tsimpoukelis, Maria Anastasia Daskalaki, Christina Trakateli, Nana Kojo Koranteng, Nikolaos Thomakos, Panagiotis Antsaklis, Dimitrios Loutradis, Georgios Daskalakis","doi":"10.3390/cimb48040429","DOIUrl":"https://doi.org/10.3390/cimb48040429","url":null,"abstract":"<p><p>Conventional hormonal and clinical models inadequately clarify the complex and diverse aspects of female infertility, resulting in poor reproductive outcomes and reduced egg viability. A growing body of research indicates that female reproductive failure is mostly due to disruptions in cellular homeostasis, especially concerning organelle quality control. Oxidative stress has emerged as a crucial mediator connecting metabolic, inflammatory, and ageing-related processes to ovarian failure, however its downstream impacts on intracellular organelle turnover remain insufficiently clarified. Our narrative review encapsulates the existing data for a unified pathogenic concept focused on the redox-regulated mitochondria-lysosome axis. We examine the interaction of oxidative stress, mitochondrial malfunction, compromised mitophagy, and lysosomal deficiency in granulosa cells and oocytes. Prolonged oxidative stress may disrupt this equilibrium, leading to defective mitochondria accumulation and impaired mitophagy. This self-perpetuating cycle may ultimately jeopardises reproductive viability and oocyte integrity. The integrated axis offers a shared molecular foundation for various infertility-related diseases, such as inadequate ovarian response, obesity-associated infertility, polycystic ovary syndrome, and ovarian ageing. Ultimately, we analyse new findings suggesting that specific antioxidant chemicals modify mitophagy and lysosomal function while also neutralising reactive oxygen species, highlighting their potential use in precision fertility treatments. Our research redefines female infertility as a condition of redox-dependent organelle quality control, thereby introducing novel avenues for identifying biomarkers, categorising patients, and targeting treatments in assisted reproduction.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"48 4","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13115354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147765079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microglial Innate Immune Memory: Implications and Research Advances in Central Nervous System Disorders.","authors":"Yaru Song, Shiyi Shu, Xiansi Zeng, Manli Xia, Junru Liu, Li Li","doi":"10.3390/cimb48040426","DOIUrl":"https://doi.org/10.3390/cimb48040426","url":null,"abstract":"<p><p>The central nervous system (CNS), comprising the brain and spinal cord, represents the core regulatory hub of the body. Damage to the CNS often leads to irreversible structural and functional impairments of neural tissues, posing a major global public health challenge. Immune memory encompasses two states: immune training and immune tolerance, which are characterized by enhanced or attenuated immune responses, respectively, following initial exposure to external stimuli in immune cells such as monocytes and macrophages. Microglia, the resident immune cells of the CNS, can be rapidly activated by external stimuli. Accumulating evidence indicates that microglial immune memory plays a critical role in sustaining states and neuroinflammatory responses in CNS disorders. Specifically, the immune training state promotes amyloid-β (Aβ) accumulation in the brains of Alzheimer's disease (AD) model mice, thereby exacerbating neuronal damage, whereas the immune tolerance state suppresses pro-inflammatory cytokine expression and alleviates neuroinflammation. This review focuses on two immune memory states in microglia-training and tolerance-and what triggers them. We summarize their roles and mechanisms in CNS diseases. Specifically, we break down how epigenetic and metabolic reprogramming control microglial immune memory, with an emphasis on how these two processes interact during memory formation and maintenance. Our goal is to fill key knowledge gaps about their combined effects and to suggest new therapeutic targets. Evidence shows that immune memory acts as a \"double-edged sword\" in the CNS: it can either fuel harmful inflammation and worsen damage, or, when moderately activated, protect nerves. Therefore, precisely balancing these two states could help reduce harmful inflammation while preserving the protective functions of microglia, offering a new, reversible immunotherapy for CNS diseases.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"48 4","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13114634/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic and Transcriptomic Pathways Underlying Animal Models of Cognitive and Psychiatric Disorders: A Scoping Review.","authors":"Jaishriram Rathored, Ajay Pal, Deepika Sai Painkra","doi":"10.3390/cimb48040425","DOIUrl":"https://doi.org/10.3390/cimb48040425","url":null,"abstract":"<p><p><b>Background:</b> Cognitive and psychiatric disorders are caused by a complex interplay between genetic predisposition, environmental exposures, and dynamic molecular regulation in the brain. Animal models provide a controlled environment for examining these mechanisms, and advances in transcriptome and epigenomic technologies have greatly expanded our knowledge of disease-relevant pathways. <b>Objective:</b> This scoping review systematically maps and synthesizes the epigenetic and transcriptomic findings from the established animal models of four neuropsychiatric conditions-autism spectrum disorder (ASD), schizophrenia, depression, and Rett syndrome-drawing on a PRISMA-ScR-guided literature search. The review characterizes the breadth of evidence, identifies convergent and divergent molecular pathways, and highlights the translational gaps and therapeutic implications. <b>Methods:</b> Research employing chromatin accessibility testing, genome-wide DNA methylation mapping, single-cell and bulk RNA sequencing, histone modification profiling, and multi-omics integration in mouse and other validated animal models was thoroughly reviewed. A quality appraisal of the primary experimental studies (n = 63) was performed using a modified CAMARADES checklist. <b>Results:</b> Beyond generalized cellular stress responses, multi-omics analysis emphasizes the cell-type- and context-dependent nature of epigenetic changes in animal models, including isoform-specific histone modifications and model-dependent binding of HDAC/MeCP2 complexes to genes involved in synaptic plasticity. Single-cell RNA sequencing analyses have uniformly shown transcriptional changes in parvalbumin-positive (PV+) interneurons. <b>Conclusions:</b> The specific convergence of epigenetic disruptions in neural circuits involved in synaptic structure and inhibitory function could play a role in the generation of neuropsychiatric phenotypes in animal models, highlighting the importance of circuit- and cell-type-specific epigenetics while pointing to potential therapeutic avenues.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"48 4","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13115134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147764027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Influence of TDP1 Inhibitor Usnic Acid Derivative OL9-116 on the Effects of Topotecan in Human Cells.","authors":"Tatyana E Kornienko, Arina A Chepanova, Maria V Kolobenko, Irina A Chernyshova, Alexandra L Zakharenko, Artur S Venzel, Nadezhda S Dyrkheeva, Andrey V Markov, Rashid O Anarbaev, Konstantin N Naumenko, Olga A Luzina, Nariman F Salakhutdinov, Vladimir A Ivanisenko, Olga I Lavrik","doi":"10.3390/cimb48040428","DOIUrl":"https://doi.org/10.3390/cimb48040428","url":null,"abstract":"<p><p>Tyrosyl-DNA phosphodiesterase 1 (TDP1) is a key enzyme for the repair of stalled topoi-somerase 1 (TOP1)-DNA complexes. We have previously developed a TDP1 inhibitor, compound OL9-116, which is capable of enhancing the action of the anticancer drug topotecan (TPC), a TOP1 poison, in vitro and in vivo. In this study, the inhibition mode of OL9-116 (uncompetitive) was investigated. We have shown that N-terminal domain of TDP1, which is important for the cell function of TDP1 but is not involved in catalysis directly, reduced the inhibitory potency of OL9-116 probably by influencing the conformation of the enzyme. OL9-116 did not reduce cell viability and did not affect mitochondrial membrane potential. OL9-116 enhanced the cytotoxic/antiproliferative effect of TPC on the panel of tumor cells. This effect was not observed on nontumor cells or TDP1-deficient cells. OL9-116 and TPC had different effects on <i>TDP1</i> and <i>TOP1</i> gene expression detected by PCR depending on the cell type and the presence of functional TDP1. The direct relation between the effects of the compounds on the gene expression and cell survival was not found. The obtained data indicated a synergistic effect of OL9-116 and TPC, which appeared to be mediated by TDP1 inhibition rather than by an effect on <i>TDP1</i> gene expression.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"48 4","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13114712/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of Serum ELMO-3 Levels with Metastatic Status and Survival Outcomes in Non-Small Cell Lung Cancer.","authors":"Hilal Oğuz Soydinç, Murat Serilmez, Ceren Tilgen Yasasever, Elif Bilgin Doğru, Uğur Gezer, Şule Karaman, Nergiz Dağoğlu Sakin, Derya Duranyıldız","doi":"10.3390/cimb48040427","DOIUrl":"https://doi.org/10.3390/cimb48040427","url":null,"abstract":"<p><p>Non-small cell lung cancer remains one of the leading causes of cancer-related mortality worldwide, and identifying molecular markers associated with tumor progression and metastasis is important for improving patient management. This study investigated serum ELMO-3 levels in patients with NSCLC and evaluated their relationship with clinicopathological characteristics. Serum samples from 50 NSCLC patients and 20 healthy controls were analyzed. ELMO-3 concentrations were measured using an enzyme-linked immunosorbent assay. Statistical analyses included non-parametric group comparisons, receiver operating characteristic curve analysis, Kaplan-Meier survival analysis, and multivariate Cox proportional hazards regression. The mean ELMO-3 level was 0.409 ± 0.543, which was used as the cutoff value to categorize patients into low- and high-ELMO-3 groups; 76% of patients were classified as low-ELMO-3 and 24% as high-ELMO-3. The results showed that serum ELMO-3 levels did not differ significantly between NSCLC patients and healthy controls and were not associated with metastatic status. However, a significant association was observed between ELMO-3 expression status and tumor histopathology. Survival analysis demonstrated that distant metastasis and radiotherapy were significantly associated with overall survival. In multivariate analysis, age, operability, distant metastasis, and serum ELMO-3 levels were identified as independent factors associated with survival. These findings suggest that circulating ELMO-3 may have potential prognostic relevance; however, the results should be interpreted with caution and require validation in larger, independent cohorts.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"48 4","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13115388/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147764905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Coptis chinensis</i> Franch. Suppresses Invasive Pulmonary Aspergillosis by Augmenting NADPH-Dependent Neutrophil Extracellular Traps via Dual Modulation of Complement Activation and Gut Microbiota.","authors":"Zhuqiao Jiang, Lingmei Zhou, Jinping Wang, Hao Sun, Liwen Cai, Hanqi Yin, Hui Zhu, Ming Li, Zhuoya Wang","doi":"10.3390/cimb48040424","DOIUrl":"https://doi.org/10.3390/cimb48040424","url":null,"abstract":"<p><p>Invasive pulmonary aspergillosis (IPA) poses a serious threat to immunocompromised hosts, with limited therapeutic options highlighting the need for novel strategies. <i>Coptis chinensis</i> Franch. (CCF), a traditional Chinese herb containing antimicrobial alkaloids like berberine, was investigated for its therapeutic efficacy and immunological effects in a murine IPA model. Immunosuppressed female KM mice infected with <i>Aspergillus fumigatus</i> AF293 were treated with CCF or amphotericin B (AmB). CCF significantly improved survival, reduced fungal burden, and alleviated lung pathology, without inducing hepatotoxicity or nephrotoxicity. Transcriptomic profiling revealed a time-dependent immune response. Complement-related pathways were enriched at 2 days post-infection, whereas neutrophil recruitment and NET-related pathways became more prominent by day 4. Hub gene analysis identified Syk, Rac2, Ncf1, and Cybb as key nodes associated with the NADPH oxidase complex. Western blot and inhibitor experiments further supported the involvement of this pathway in CCF-mediated protection. Additionally, 16S rDNA sequencing indicated enrichment of <i>Clostridium</i> species in the gut microbiota of CCF-treated mice, which was positively correlated with the expression of NADPH oxidase-related genes, suggesting a potential gut-lung association. In conclusion, these findings support the antifungal efficacy of CCF in IPA and suggest that its protective effects may involve coordinated changes in complement-related responses, NADPH oxidase-associated neutrophil activity, and gut microbiota composition.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"48 4","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13115011/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147764857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mining and Analysis of Salt Tolerance Genes in Maize at the Seedling Stage.","authors":"Zhenping Ren, Zelong Zhuang, Jianwen Bian, Wanling Ta, Xiaojia Hao, Lei Zhang, Yunling Peng","doi":"10.3390/cimb48040423","DOIUrl":"https://doi.org/10.3390/cimb48040423","url":null,"abstract":"<p><p>Salt stress represents a significant abiotic stress factor that adversely affects plant growth and development. It directly inhibits both vegetative and reproductive growth, resulting in substantial reductions in crop yield and quality. Consequently, the identification of salt tolerance genes and the elucidation of their underlying molecular mechanisms are crucial for improving crop salt tolerance and ensuring agricultural productivity. To investigate the molecular basis underlying differential salt tolerance between Zheng58 and PH4CV, we employed pooled sequencing (BSA-seq) using extreme phenotypic individuals from their F₂ population and conducted a comparative transcriptome analysis at the seedling stage of the two genotypes. Phenotypic, physiological, biochemical, and ion content analyses revealed that Zheng58 exhibited significantly superior performance compared to PH4CV under salt stress conditions. BSA-seq analysis identified six genomic regions associated with salt tolerance, encompassing a total of 391 genes. Functional annotation enabled the screening of 151 candidate genes potentially involved in salt stress responses. Transcriptome profiling indicated that differentially expressed genes were significantly enriched in biological processes, particularly plant hormone signal transduction and MAPK signaling pathways. Integrating BSA-seq and transcriptome data, key candidate gene <i>ZmACC2</i> (<i>Zm00001eb419400</i>) was identified as potentially involved in the regulation of salt tolerance in maize. This gene may modulate Na⁺/K⁺/Ca²⁺ homeostasis and reactive oxygen species metabolism through defense responses mediated by ethylene (ETH) and hydrogen peroxide, as well as through ion homeostasis regulatory pathways. This study provides valuable candidate genes and a theoretical foundation for further dissection of the molecular mechanisms governing salt tolerance in maize.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"48 4","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13115532/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Genetics of Bartter Syndrome: Bridging Genotype-Phenotype Correlations and Precision Therapeutics.","authors":"Lina Zhu, Yang Li, Yiyao Bao","doi":"10.3390/cimb48040422","DOIUrl":"https://doi.org/10.3390/cimb48040422","url":null,"abstract":"<p><p>Bartter syndrome (BS) represents a group of rare, autosomal recessive renal tubular disorders characterized by hypokalemic hypochloremic metabolic alkalosis, secondary hyperaldosteronism, and normal to low blood pressure. The underlying pathophysiology is primarily driven by defects in critical ion transport proteins or channels localized within the thick ascending limb of the loop of Henle, leading to impaired salt reabsorption. Recent advances in molecular genetics have refined the classification of Bartter syndrome. Current evidence supports SLC12A1, KCNJ1, CLCNKB, BSND, and MAGED2 as the core disease genes within the contemporary BS spectrum, with MAGED2 causing a distinct X-linked transient antenatal form. In contrast, gain-of-function CASR variants, historically labeled \"type V Bartter syndrome\", are now more appropriately described as CaSR-associated Bartter-like phenotypes within the broader spectrum of disorders of calcium homeostasis. Despite significant progress, two primary research limitations remain. First, fully elucidating genotype-phenotype correlations and overcoming diagnostic complexities continues to be highly challenging due to substantial phenotypic overlap and genetic heterogeneity. Compounding these diagnostic hurdles is the equally critical challenge of understanding mutation-driven pathogenic mechanisms to develop viable clinical interventions. This review systematically summarizes the current molecular genetic landscape of BS to address these gaps. We highlight the relationships between specific genetic variants and clinical manifestations, delve into molecular pathophysiology including protein misfolding and trafficking defects, and explore emerging therapeutic approaches such as molecular chaperones. By integrating genetic and clinical data, this work aims to provide a comprehensive framework to facilitate precise diagnosis and individualized treatment strategies, ultimately advancing precision medicine in the management of Bartter syndrome.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"48 4","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13114623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147764680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Management of Pregnancy in Women with Inflammatory Bowel Disease: Positioning Janus Kinase Inhibitors Within Current Evidence.","authors":"Dario Colacurci, Raffaele Pellegrino, Alessia Lamart, Davide Staiano, Ilaria De Costanzo, Michele Izzo, Giuseppe Imperio, Fabio Landa, Giulia Scamardella, Enrica Di Lella, Alessandro Federico, Laura Sarno, Antonietta Gerarda Gravina","doi":"10.3390/cimb48040421","DOIUrl":"https://doi.org/10.3390/cimb48040421","url":null,"abstract":"<p><p>Inflammatory bowel diseases (IBD) frequently affect women of reproductive age. Disease activity may arise during pregnancy, at times in severe forms, thereby generating complex clinical scenarios. Adequate control of disease activity throughout pregnancy and the achievement of a safe delivery with a healthy newborn, therefore, represent vital objectives in therapeutic management. In recent years, the therapeutic armamentarium for moderate to severe IBD has expanded exponentially, with the introduction of biological agents and small molecules. However, although these therapies have largely superseded conventional treatment in complex settings, they do not share the same safety profile in pregnancy. Concerns persist regarding potential transplacental transfer and possible teratogenic effects, which justify mandatory caution in their use during pregnancy. Nonetheless, clinicians may readily encounter scenarios of active IBD during pregnancy in patients who have previously experienced failure of the biological agents most extensively studied in this context, thus necessitating an evaluation of the safety of more novel therapeutic options. This review examines the available evidence on Janus kinase inhibitors. Current data, which are highly heterogeneous and of low quality, preclude any recommendation for the use of these small molecules during pregnancy. Prospective registries and large-scale observational studies are mandatory, pending the feasibility of dedicated trials, to better characterise these inhibitors, which could prove valuable, should the evidence ultimately support their use, in women with biologic multi-failure active IBD during pregnancy.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"48 4","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13114786/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147765135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Challenges and Limitations in Molecular Testing of Resected Non-Small Cell Lung Cancer Specimens.","authors":"Nikolaos Korodimos, Ioannis Tomos, Periklis Foukas, Konstantinos Kontzoglou, Anna Koumarianou, Ilias Santaitidis, Konstantinos Kostopanagiotou, Sofoklis Mitsos, Anastasios Moisiadis, Periklis Tomos","doi":"10.3390/cimb48040419","DOIUrl":"https://doi.org/10.3390/cimb48040419","url":null,"abstract":"<p><p>Non-small cell lung cancer (NSCLC) accounts for nearly 85% of lung cancer cases and remains a leading cause of cancer-related mortality worldwide. Advances in molecular diagnostics and targeted therapies have transformed treatment paradigms, yet the integration of molecular testing into routine care for resected NSCLC specimens continues to face significant challenges. This review outlines the technical, clinical, and systemic barriers that limit the effectiveness of molecular testing. Key considerations include tissue quality, the limitations of formalin-fixed paraffin-embedded (FFPE) samples, and the comparative roles of conventional methods-such as immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and reverse transcription polymerase chain reaction (RT-PCR)-versus next-generation sequencing (NGS). We also discuss the prevalence and clinical relevance of common genomic alterations, including TP53, KRAS, EGFR, and ALK, as well as their impact on prognosis and treatment selection. Real-world obstacles such as accessibility, reimbursement, delays in testing, interdisciplinary coordination, and sample adequacy are critically examined. Emerging innovations-including multi-omics integration, spatial profiling, liquid biopsy, artificial intelligence, and novel targeted therapies-offer opportunities to overcome current limitations and improve patient outcomes. Finally, practical recommendations are proposed to optimize tissue handling, testing algorithms, and access to precision-guided therapies. By addressing these challenges, molecular testing in NSCLC can be more effectively leveraged to personalize treatment strategies and enhance survival outcomes.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"48 4","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13115249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147765000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}