Exploration of targeted anti-tumor therapy最新文献

{"title":"Dysbiosis and colorectal cancer: conducive factors, biological and molecular role, and therapeutic prospectives.","authors":"Gurkaranjot Singh, Zuhair Chaudhry, Anik Boyadzhyan, Kayvan Sasaninia, Vikrant Rai","doi":"10.37349/etat.2025.1002329","DOIUrl":"10.37349/etat.2025.1002329","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is the third leading cause of cancer-related death in the United States. Emerging evidence highlights the significant role of gut microbiota dysbiosis, characterized by a reduction in beneficial bacteria and an increase in pro-inflammatory and pro-carcinogenic bacteria, in CRC pathogenesis. Both genetic and environmental factors, including diet, antibiotic use, physical activity, aging, and obesity, contribute to this microbial imbalance. Dysbiosis promotes chronic inflammation and immune dysregulation, which facilitates tumor initiation and progression. This review examines the intricate interactions between gut microbiota, immune modulation, and CRC development. It explores current and emerging therapeutic strategies that target the microbiome to enhance treatment efficacy, discusses interventions aimed at restoring healthy microbiota in CRC patients, and outlines future directions for microbiome-based therapies to improve clinical outcomes.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"6 ","pages":"1002329"},"PeriodicalIF":0.0,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203119/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144531396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biliary tract cancers: advances in diagnostic and management.","authors":"James Gutmans, Hiba Mechahougui","doi":"10.37349/etat.2025.1002328","DOIUrl":"10.37349/etat.2025.1002328","url":null,"abstract":"<p><p>Biliary tract cancers (BTCs) are aggressive malignancies associated with poor prognosis and limited treatment options. Advances in precision oncology, notably the identification of recurrent molecular alterations such as fibroblast growth factor receptor 2 (<i>FGFR2</i>) fusions, isocitrate dehydrogenase 1 (<i>IDH1</i>) mutations, <i>ERBB2</i> amplifications, and v-Raf murine sarcoma viral oncogene homolog B (<i>BRAF</i>) V600E mutations, have introduced new therapeutic avenues and modest survival benefits for patients with advanced disease. However, the practical implementation of targeted therapies remains hampered by challenges in tumor tissue acquisition and molecular testing, highlighting the need for alternative genomic profiling strategies. This comprehensive review examines the role of liquid biopsy as a non-invasive strategy for molecular profiling in BTCs, with a focus on the clinical applications of plasma and bile-derived circulating tumor DNA (ctDNA). We synthesized findings from recent clinical studies evaluating mutation detection rates, concordance between liquid biopsy and tissue-based assays, and the comparative performance of plasma versus bile ctDNA. Liquid biopsy demonstrates high rates of mutation detection and good concordance with tissue analyses. Bile-derived ctDNA, owing to its proximity to the tumor, consistently shows higher sensitivity and mutant allele frequencies (MAFs) than plasma ctDNA. Nevertheless, challenges remain, including lower sensitivity for detecting structural alterations (e.g., gene fusions), variability in ctDNA yield depending on disease status, and a lack of assay standardization across platforms. Liquid biopsy, particularly through bile ctDNA analysis, emerges as a promising adjunct to tissue biopsy for molecular profiling in BTCs. It offers opportunities for earlier, less invasive, and more personalized treatment decisions. Future directions should aim at developing tumor-informed liquid biopsy strategies that increase precision, reduce costs, and ultimately improve patient outcomes. Prospective studies are needed to confirm its clinical utility and survival impact.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"6 ","pages":"1002328"},"PeriodicalIF":0.0,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144531395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Future perspectives: targeting fibroblast growth factor receptor 1 to enhance the efficacy of immunotherapy.","authors":"Ilya Tsimafeyeu","doi":"10.37349/etat.2025.1002327","DOIUrl":"10.37349/etat.2025.1002327","url":null,"abstract":"<p><p>Fibroblast growth factor receptor 1 (FGFR1) plays a critical role in the progression of various cancers through its involvement in cell proliferation, survival, and differentiation. More recently, FGFR1 has been implicated in the mechanisms of immune evasion, particularly its role in resistance to immune checkpoint inhibitors (ICIs) such as pembrolizumab and nivolumab. Targeting FGFR1 with monoclonal antibodies and tyrosine kinase inhibitors has emerged as a promising therapeutic strategy to enhance ICI efficacy by altering the tumor microenvironment and countering immune suppression. Preclinical studies demonstrate that combining FGFR1 inhibitors, such as the novel monoclonal antibody OM-RCA-01, with ICIs significantly improves antitumor activity, enhancing T cell responses and cytokine production. This article explores the role of FGFR1 in cancer biology, its contribution to immunotherapy resistance, and the therapeutic potential of targeting FGFR1 to enhance the efficacy of ICIs.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"6 ","pages":"1002327"},"PeriodicalIF":0.0,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12179639/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144478091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An overview of the feasibility of nanomedicine in pancreatic cancer theranostics.","authors":"Kyriakos Kokkinogoulis, Aristomenis Kollas, David Simeonidis, Pavlos Papakostas, Kalliopi Platoni, Efstathios P Efstathopoulos, Mersini Makropoulou","doi":"10.37349/etat.2025.1002326","DOIUrl":"10.37349/etat.2025.1002326","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) is among the top causes of cancer-induced mortality, frequently diagnosed too late to be treated effectively, due to the poor prognosis and the limited successful therapeutic options. Apart from the conventional treatments, new multimodal therapies have emerged utilizing different scientific fields for the improvement of the survival and quality of patients' lives. The advancement of nanotechnology leads the way to more personalized medicine and the use of targeted theranostics carriers for deep-seated cancers such as PDAC. New nanotechnology innovations such as specialized photo-sensitizing drug nanocarriers, can effectively improve photodynamic therapy (PDT) of PDAC and enhance phototherapy's action through surface plasmon resonance phenomenon, as another recently re-emerged non- or minimally invasive possible treatment of such diseases. Despite the scientific advancements, significant hurdles remain and many parameters need to be examined. However, the novel application of nano-biophotonic techniques and the convergence of different science fields offer promise for the treatment of difficult-to-treat diseases, like PDAC.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"6 ","pages":"1002326"},"PeriodicalIF":0.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12179641/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144478066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of outcomes of neoadjuvant chemotherapy in <i>BRCA1</i>- versus <i>BRCA2</i>-associated breast and ovarian cancers.","authors":"Anna Sokolenko, Tatiana Gorodnova, Diana Enaldieva, Anna Shestakova, Alexandr Ivantsov, Anna Nyuganen, Igor Berlev, Petr Krivorotko, Alexey Belyaev, Evgeny Imyanitov","doi":"10.37349/etat.2025.1002325","DOIUrl":"10.37349/etat.2025.1002325","url":null,"abstract":"<p><strong>Aim: </strong><i>BRCA1</i>/<i>2</i>-associated breast and ovarian carcinomas are often regarded as a single entity, assuming that <i>BRCA1</i> and <i>BRCA2</i> genes are almost equivalent with regard to their clinical significance. However, <i>BRCA1</i> and <i>BRCA2</i> genes differ in their function; therefore, a comparison of treatment outcomes in <i>BRCA1</i> vs. <i>BRCA2</i> carriers is warranted.</p><p><strong>Methods: </strong>This study focused on consecutive patients treated with neoadjuvant chemotherapy (NACT), given that these subjects are treatment-naive and accessible for immediate assessment of pathological and clinical outcomes.</p><p><strong>Results: </strong><i>BRCA2</i>-associated high-grade serous ovarian carcinomas (HGSOCs) demonstrated significantly higher rates of pathologic complete response (pCR) as compared to <i>BRCA1</i>-related cancers [8/15 (53%) vs. 7/48 (15%), <i>P</i> = 0.004]. In contrast, HER2-negative breast cancer (BC) patients showed a numerically higher rate of pCR in <i>BRCA1</i> vs. <i>BRCA2</i> mutation carriers [38/69 (55%) vs. 13/36 (36%), <i>P</i> = 0.1]. However, the comparison with <i>BRCA-</i>wild-type (WT) tumors revealed that this tendency was mainly attributed to the increased prevalence of hormone receptor (HR)-negative disease in the former group. When BC patients were stratified according to the tumor receptor status, the response rates in triple-negative patients were consistently higher than in HR+/HER2- patients across all analyzed subgroups [<i>BRCA1</i>: 35/59 (59%) vs. 3/10 (30%); <i>BRCA2</i>: 5/10 (50%) vs. 8/26 (31%); WT: 31/76 (41%) vs. 12/74 (16%); Mantel-Haenzsel <i>P</i> < 0.001]. Logistic regression analysis revealed that the odds ratio (OR) for achieving pCR was higher for receptor status (triple-negative vs. HR+: OR = 3.4, 95% CI 1.9-6.0, <i>P</i> < 0.001) than for <i>BRCA</i> status (any mutation vs. WT: OR = 2.1, 95% CI 1.2-3.6, <i>P</i> = 0.008). The addition of carboplatin did not improve pCR rates in <i>BRCA1</i>- or <i>BRCA2</i>-associated BCs, while there was a numerically higher efficacy of carboplatin-containing regimens in patients with WT triple-negative tumors [14/26 (54%) vs. 15/44 (34%), <i>P</i> = 0.13].</p><p><strong>Conclusions: </strong>Hereditary ovarian carcinomas demonstrate better NACT outcomes in <i>BRCA2</i> vs. <i>BRCA1</i> mutation carriers. The opposite trend is observed in BC, which is likely to be attributed to a high frequency of triple-negative disease in <i>BRCA1</i>- but not <i>BRCA2</i>-associated BCs. Triple-negative receptor status rather than <i>BRCA1</i>/<i>2</i> status is the strongest predictor of response to NACT in BC.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"6 ","pages":"1002325"},"PeriodicalIF":0.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12179429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144478067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Osteosarcoma: current insights and advances.","authors":"Guraustin S Brar, Aidan A Schmidt, Logan R Willams, Mark R Wakefield, Yujiang Fang","doi":"10.37349/etat.2025.1002324","DOIUrl":"10.37349/etat.2025.1002324","url":null,"abstract":"<p><p>Osteosarcoma is the most prevalent primary malignant bone tumor affecting adolescents and young adults. Despite advancements in cancer therapies, its prognosis remains poor due to its aggressive nature and early propensity for metastasis-often present at the time of diagnosis. The etiology of osteosarcoma is multifactorial, involving genetic predispositions, environmental exposures, and familial syndromes. While treatment strategies are largely dictated by tumor stage, neoadjuvant chemotherapy followed by surgical resection remains the cornerstone of management. This review provides a comprehensive overview of osteosarcoma, including its historical context, subclassifications, clinical presentation, diagnostic approaches, and evolving treatment modalities. Recent therapeutic innovations-such as gene therapy, immunotherapy, radiation advances, and tyrosine kinase inhibitors-are discussed in detail, highlighting their mechanisms and clinical potential. By synthesizing current literature and identifying ongoing challenges, this review aims to inform clinicians and researchers of recent progress while highlighting critical gaps to guide future research and improve patient outcomes in osteosarcoma care.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"6 ","pages":"1002324"},"PeriodicalIF":0.0,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12179640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144478092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mutational landscape of epidermoid carcinoma of the penis in a Brazilian cohort.","authors":"Renato Mendes Rossi De Lucca, Danielle Barbosa Brotto, Claudia Tarcila Gomes Sares, Kelly Gomes Duarte, Wilson Araujo Silva Junior, Philippe E Spiess, Shahrokh F Shariat, Natália Dalsenter Avilez, Caio de Oliveira, Leonardo O Reis, Rodolfo Borges Dos Reis","doi":"10.37349/etat.2025.1002323","DOIUrl":"10.37349/etat.2025.1002323","url":null,"abstract":"<p><strong>Aim: </strong>Penile cancer (PeCa) is a rare malignancy strongly associated with poor genital hygiene and is more prevalent in regions with low socioeconomic status. PeCa accounts for approximately 2% to 4% of all male cancers in Brazil, with higher incidence in the North and Northeast regions. Despite its aggressive nature, the molecular mechanisms underlying PeCa remain poorly understood. We performed whole-exome sequencing in a Brazilian cohort of patients with PeCa to identify potentially pathogenic genetic alterations associated with tumor development and progression.</p><p><strong>Methods: </strong>Tumor tissue samples were obtained from patients diagnosed with PeCa. DNA was extracted and subjected to whole-exome sequencing. Human papillomavirus (HPV) genotyping was performed for subtypes 16 and 18. Control samples were collected from individuals without PeCa or other genital diseases.</p><p><strong>Results: </strong>The cohort demonstrated considerable genetic heterogeneity. Multiple gene mutations were identified in tumor samples, many of which are involved in carcinogenesis-related biological pathways. Distinct molecular profiles were observed, suggesting diverse tumorigenic mechanisms. <i>MUC16</i> (present in 11/12 patients, 91.7%) and <i>PABPC1</i> (8/12 patients, 66.7%) were the most frequently mutated genes. HPV-16 was detected in a subset of cases; however, no consistent association with more aggressive disease was identified.</p><p><strong>Conclusions: </strong>This study provides new insights into the genomic landscape of PeCa in a Brazilian population. The findings highlight the presence of heterogeneous and potentially pathogenic mutations, reinforcing the need for further molecular characterization and exploration of novel therapeutic targets in PeCa.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"6 ","pages":"1002323"},"PeriodicalIF":0.0,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12142355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of exosomes in transforming growth factor-β-mediated cancer cell plasticity and drug resistance.","authors":"Tatiana Ruksha, Nadezhda Palkina","doi":"10.37349/etat.2025.1002322","DOIUrl":"10.37349/etat.2025.1002322","url":null,"abstract":"<p><p>Transforming growth factor-β (TGF-β) is a multifunctional molecule with a dual role in carcinogenesis. Recent studies have demonstrated its various effects on cancer-related processes. However, the identification of TGF-β and TGF-β signaling pathway regulators in extracellular vesicles (EVs) appears promising for targeting them to control cancer progression associated with drug resistance. Exosomal TGF-β has been shown to be implicated in cancer cell phenotypic plasticity, a dynamic feature of cancer cells, and an evasive process hampering treatment efficacy. Additionally, EVs can influence the metastatic cascade through mechanisms, including their effects on the immune system and their binding to extracellular matrix (ECM) proteins. These processes collaborate to provide a supportive microenvironment for the development and growth of metastatic tumors. A deeper understanding of the mechanisms by which EVs facilitate TGF-β-mediated intercellular communication may have practical implications for better controlling oncological disorders and providing new methods for cancer diagnostics and treatment, including approaches targeting EVs.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"6 ","pages":"1002322"},"PeriodicalIF":0.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12142356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating tumor cells: overcoming challenges of detecting a needle in a haystack.","authors":"Zhuldyz Myrkhiyeva, Kuanysh Seitkamal, Zhannat Ashikbayeva, Assiya Taizhanova, Daniele Tosi, Aliya Bekmurzayeva","doi":"10.37349/etat.2025.1002321","DOIUrl":"10.37349/etat.2025.1002321","url":null,"abstract":"<p><p>Circulating tumor cells (CTCs) are cancer cells that are detached from the primary and metastatic tumor site and invade the bloodstream. Most importantly, CTCs are the key players in the development of metastasis. As one of the main components of liquid biopsy, they may significantly contribute to improvements in early cancer diagnosis, monitoring response to therapy, and predicting recurrence of the disease. Although identifying and analyzing CTCs offers the potential for a real-time liquid biopsy, their detection is associated with a number of challenges, which mainly stem from three sources: complexity of the CTCs, complexity of the media (blood), and performance of the detection assays. Particularly, low concentration of the CTCs and the presence of a vast population of hematopoietic cells in the blood make their detection technically complex. The heterogeneity of the target cells and not enough sensitivity of the measuring platforms are also among major technical challenges in CTC detection. Therefore, this review aims to give an update on various methods developed for CTC isolation, including chip-based assays and biosensors. The work will elucidate various challenges associated with the isolation and detection of CTCs and showcase the studies that aimed to tackle them. A number of available commercial platforms for CTC detection and hurdles associated with their widespread applications in clinical settings will also be discussed.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"6 ","pages":"1002321"},"PeriodicalIF":0.0,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12123222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144200982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A viral circular RNA in Kaposi's sarcoma-associated herpesvirus modulates viral and host gene expression during latent and lytic replication.","authors":"Soleil Torres, Vaibhav Jain, Daniel Stribling, Lauren A Gay, Muhammed Naeem, Melody Baddoo, Erik K Flemington, Scott A Tibbetts, Rolf Renne","doi":"10.37349/etat.2025.1002320","DOIUrl":"10.37349/etat.2025.1002320","url":null,"abstract":"<p><strong>Aim: </strong>Circular RNA (circRNA) is a class of noncoding, single-stranded RNA generated by backsplicing, a process where the 5' and 3' ends of an RNA are covalently joined. Virally encoded circRNAs have been identified in several members of Gammaherpesvirinae, including Kaposi's sarcoma-associated herpesvirus (KSHV). In KSHV, the viral interferon regulatory factor 4 (vIRF4) region produces two isoforms of circRNA (circ-vIRF4) that are detectable during latency and reactivation. Given the growing literature implicating circRNA in human diseases, a role may exist for circ-vIRF4 in the development of KSHV malignancies. Therefore, the aim of this study is to characterize the function of vIRF4 circRNAs.</p><p><strong>Methods: </strong>A KSHV mutant (Δcirc-vIRF4) was generated in the BAC16 bacmid and transfected into 293T and iSLK cells. Expression of circRNA after mutagenesis was assessed by qualitative and quantitative PCR. Host and viral gene expression in iSLK cells during both viral latency and reactivation were also assessed by RNA-seq.</p><p><strong>Results: </strong>RT-PCR of Δcirc-vIRF4-infected iSLK cells demonstrated no expression of wild-type (WT) isoforms, but PCR cloning showed that alternative backsplice sites were used to express novel vIRF4 circRNAs, where the most prominent isoform was a 1,020 nt isoform. RNA-seq analyses comparing WT- and Δcirc-vIRF4-infected iSLK cells demonstrated significant differential expression of both host and viral genes during both phases of the viral life cycle. Gene ontology analyses returned terms related to cell adhesion, proliferation, and migration for both datasets, as well as kinase signaling and apoptosis for the lytic dataset.</p><p><strong>Conclusions: </strong>These results show that KSHV can switch to an alternative backsplice site for vIRF4 circRNA production in the absence of a canonical splice site and that circ-vIRF4 contributes to the regulation of both host and viral gene expression through an unknown mechanism.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"6 ","pages":"1002320"},"PeriodicalIF":0.0,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12123221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144200981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}