Exploration of targeted anti-tumor therapy最新文献

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Dendritic cell-based immunotherapy modulates the systemic inflammatory profile in a 4T1 breast cancer model. 基于树突状细胞的免疫疗法调节4T1乳腺癌模型的全身炎症谱。
Exploration of targeted anti-tumor therapy Pub Date : 2026-08-05 eCollection Date: 2026-01-01 DOI: 10.37349/etat.2026.1002393
Tauana Christina Dias, Jéssica Ferreira Vieira, Katiane Tostes, Polyana Barbosa Silva, Angela Maria Moed Lopes, Gabriela Karam Rebolho, Eddie Fernando Candido Murta, Lidia Maria Rebolho Batista Arantes, Márcia Antoniazi Michelin
{"title":"Dendritic cell-based immunotherapy modulates the systemic inflammatory profile in a 4T1 breast cancer model.","authors":"Tauana Christina Dias, Jéssica Ferreira Vieira, Katiane Tostes, Polyana Barbosa Silva, Angela Maria Moed Lopes, Gabriela Karam Rebolho, Eddie Fernando Candido Murta, Lidia Maria Rebolho Batista Arantes, Márcia Antoniazi Michelin","doi":"10.37349/etat.2026.1002393","DOIUrl":"10.37349/etat.2026.1002393","url":null,"abstract":"<p><strong>Aim: </strong>Breast cancer remains a major cause of cancer-related mortality in women, particularly in advanced stages where therapeutic options are limited. While immune checkpoint inhibitors (ICIs) have improved outcomes in a subset of patients, many do not respond, highlighting the need for alternative immunotherapeutic strategies. This study evaluated the effect of dendritic cell (DC)-based immunotherapy on tumor growth and on the inflammatory profile of peritoneal myeloid cells in a 4T1 murine breast cancer model.</p><p><strong>Methods: </strong>BALB/c mice bearing 4T1 breast tumors were treated with bone marrow-derived DC-based immunotherapy. Tumor volume was monitored over time, and CD14<sup>+</sup> cells obtained from peritoneal lavage were analyzed by flow cytometry for the cytokines IL-12, IL-17, and TNF-α and the transcription factors RORγT and GATA3.</p><p><strong>Results: </strong>DC-based immunotherapy was associated with a non-significant trend toward reduced tumor volume and a marked suppression of key proinflammatory cytokines: IL-12 (<i>P</i> < 0.0005), IL-17 (<i>P</i> < 0.0001), and TNF-α (<i>P</i> < 0.0001). Expression of the transcription factors RORγT and GATA3, associated with Th17 and Th2 differentiation, was also downregulated (<i>P</i> < 0.0001). These immunological effects were observed in CD14<sup>+</sup> myeloid cells from the peritoneal compartment.</p><p><strong>Conclusions: </strong>DC-based immunotherapy modulates the systemic/peritoneal inflammatory profile and attenuates tumor-promoting inflammation. This strategy may offer therapeutic benefit for patients with breast cancer who are unresponsive to conventional or ICI-based treatments and supports its further evaluation in translational studies.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"7 ","pages":"1002393"},"PeriodicalIF":0.0,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13439114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148681220","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}
引用次数: 0
Consensus statements on the definition, diagnosis, and management of oligoprogressive disease: results of an expert survey of Kazakhstan Cancer Society. 关于少进展性疾病的定义、诊断和管理的共识声明:哈萨克斯坦癌症协会专家调查的结果。
Exploration of targeted anti-tumor therapy Pub Date : 2026-08-05 eCollection Date: 2026-01-01 DOI: 10.37349/etat.2026.1002392
Dilyara Kaidarova, Indira Omarova, Samat Kaldarbekov, Nazgul Omarbayeva, Maia Dzhugashvili, Elena Ulrikh, Dina Alisheva, Bakhadyr Bereketov, Ilya Tsimafeyeu, Timur Mitin
{"title":"Consensus statements on the definition, diagnosis, and management of oligoprogressive disease: results of an expert survey of Kazakhstan Cancer Society.","authors":"Dilyara Kaidarova, Indira Omarova, Samat Kaldarbekov, Nazgul Omarbayeva, Maia Dzhugashvili, Elena Ulrikh, Dina Alisheva, Bakhadyr Bereketov, Ilya Tsimafeyeu, Timur Mitin","doi":"10.37349/etat.2026.1002392","DOIUrl":"10.37349/etat.2026.1002392","url":null,"abstract":"<p><strong>Aim: </strong>Oligoprogressive disease (OPD) has emerged as a clinically relevant and common scenario in oncology, reflecting progression in a limited number of metastatic sites while systemic therapy continues to control the majority of disease. Despite its increasing recognition, the definition, diagnostic approach, and management of OPD remain poorly standardized.</p><p><strong>Methods: </strong>A multidisciplinary expert panel from Kazakhstan and international faculty, including ten medical oncologists, radiation, and surgical oncologists, participated in a structured survey. The questionnaire consisted of 15 items divided into three domains: definition of OPD, diagnostic evaluation, and treatment strategies. Responses were analyzed, and consensus was defined as ≥ 70% agreement, relative agreement as 50-69%, and lack of consensus as < 50%.</p><p><strong>Results: </strong>Consensus was reached that OPD is defined as progression in a limited number of lesions while other sites remain controlled, regardless of lesion size or localization. No consensus was achieved regarding the maximum number of progressive lesions, with experts divided between \"≤ 5 lesions\" and \"any number amenable to local therapy.\" Imaging with CT or PET-CT was considered sufficient. Biopsy and molecular testing were recommended only in selected contexts. Systemic therapy continuation during OPD was endorsed if effective, with strong support for local therapy, particularly stereotactic ablative radiotherapy (SBRT/SABR). Divergence remained regarding the management of repeat OPD.</p><p><strong>Conclusions: </strong>This Kazakhstan Cancer Society consensus defines the fundamental clinical features of OPD and provides practical recommendations for diagnosis and treatment. Comparison with international guidelines reveals broad alignment on systemic continuation and local therapy, as well as persistent variation regarding lesion number, biopsy, and repeat OPD management.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"7 ","pages":"1002392"},"PeriodicalIF":0.0,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13439110/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148681273","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}
引用次数: 0
Transcriptional modulation of the PI3K/AKT/mTOR signaling pathway mediated by HPV16 E5, E6, and E7 oncogene expression in breast cancer. 乳腺癌中HPV16 E5、E6、E7癌基因表达介导的PI3K/AKT/mTOR信号通路的转录调节
Exploration of targeted anti-tumor therapy Pub Date : 2026-08-04 eCollection Date: 2026-01-01 DOI: 10.37349/etat.2026.1002391
Beatriz Eda de Oliveira Isídio, Pedro Henrique Bezerra Fontes, Gabriel Rômulo Parente da Silva, Stephanie Loureiro Leão, Bianca de França São Marcos, Isabelle Silva Simões, Elisa Fotin Genn Barros, David Beltrán Lussón, Gabriela Vitória de Araujo, Isabela Duarte de Farias, Karina Mayumi Tani Bezerra de Melo, Nathálya Lima de Queiroz, Sandra Maria Souza da Silva, Vanessa Emanuelle Pereira Santos, Antonio Carlos de Freitas
{"title":"Transcriptional modulation of the PI3K/AKT/mTOR signaling pathway mediated by HPV16 <i>E5</i>, <i>E6</i>, and <i>E7</i> oncogene expression in breast cancer.","authors":"Beatriz Eda de Oliveira Isídio, Pedro Henrique Bezerra Fontes, Gabriel Rômulo Parente da Silva, Stephanie Loureiro Leão, Bianca de França São Marcos, Isabelle Silva Simões, Elisa Fotin Genn Barros, David Beltrán Lussón, Gabriela Vitória de Araujo, Isabela Duarte de Farias, Karina Mayumi Tani Bezerra de Melo, Nathálya Lima de Queiroz, Sandra Maria Souza da Silva, Vanessa Emanuelle Pereira Santos, Antonio Carlos de Freitas","doi":"10.37349/etat.2026.1002391","DOIUrl":"10.37349/etat.2026.1002391","url":null,"abstract":"<p><strong>Aim: </strong>Breast cancer is the most prevalent malignant tumor among women. Human papillomavirus (HPV) has been detected in breast tumors since the 1990s, and beyond its oncogenic potential, therapy resistance driven by viral immune evasion in non-anogenital tumors, such as oropharyngeal cancers, highlights the need to investigate viral activity in breast tissues. Among high-risk HPV types, HPV16 is one of the most prevalent and exhibits the highest carcinogenic potential. Therefore, this study aimed to evaluate the expression of HPV16 oncogenes <i>E5</i>, <i>E6</i>, and <i>E7</i> in breast tumors, as well as the modulation of the PI3K/AKT/mTOR signaling pathway associated with viral activity.</p><p><strong>Methods: </strong>A total of 92 breast cancer patients were included after Ethics Committee approval. Clinical data were obtained from medical records. RNA was extracted from formalin-fixed, paraffin-embedded tissues and reverse-transcribed into cDNA. Transcripts of HPV oncogenes (<i>E5</i>, <i>E6</i>, and <i>E7</i>), components of the PI3K/AKT/mTOR pathway, and regulatory genes (<i>EGFR</i> and <i>PTEN</i>) were quantified by RT-qPCR. Gene expression levels were calculated using the ΔCt method.</p><p><strong>Results: </strong>Forty-eight samples met RNA quality criteria and were included in the expression analysis. Among these, 77.08% showed expression of at least one viral oncogene, with <i>E5</i> being the most frequently expressed. The PI3K/AKT/mTOR pathway was modulated in HPV-positive samples, with increased PI3K expression and decreased mTOR expression. Notably, the high expression of E5-associated with immune evasion-combined with reduced mTOR expression suggests that HPV16 status may influence therapeutic response in breast cancer patients.</p><p><strong>Conclusions: </strong>These findings reinforce the importance of further studies investigating HPV activity in breast tumors to better understand its biological and clinical impact.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"7 ","pages":"1002391"},"PeriodicalIF":0.0,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13439120/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148681242","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}
引用次数: 0
Targeting tumor transition windows. 靶向肿瘤转移窗口。
Exploration of targeted anti-tumor therapy Pub Date : 2026-07-30 eCollection Date: 2026-01-01 DOI: 10.37349/etat.2026.1002390
Ola A Al-Ewaidat, Moawiah M Naffaa
{"title":"Targeting tumor transition windows.","authors":"Ola A Al-Ewaidat, Moawiah M Naffaa","doi":"10.37349/etat.2026.1002390","DOIUrl":"10.37349/etat.2026.1002390","url":null,"abstract":"<p><p>Tumor heterogeneity and cellular plasticity are major drivers of therapeutic failure across many cancer types. While precision oncology has largely focused on static genomic alterations, growing evidence indicates that tumors behave as dynamic biological systems that continuously adapt during treatment. Tumor cell populations can transition between distinct functional states under therapeutic pressure, including transient drug-tolerant phenotypes that may precede stabilization of genetically or epigenetically resistant clones. These transitions are shaped by mechanisms such as epigenetic reprogramming, stress-response signaling, metabolic rewiring, and microenvironmental interactions. This review synthesizes findings from tumor plasticity, drug-tolerant persister biology, therapy-induced vulnerabilities, clonal evolution, and adaptive therapy to examine how temporal tumor dynamics influence treatment response. Emerging evidence suggests that some tumors may pass through short-lived phases of cellular instability during therapy in which molecular dependencies, stress-response programs, or adaptive survival states are altered before resistance becomes genetically or epigenetically stabilized. However, such transition states should be considered therapeutically actionable only when linked to functional evidence of altered drug sensitivity, pathway dependence, immune susceptibility, or clinical response. Advances in single-cell transcriptomics, epigenomic profiling, serial circulating tumor deoxyribonucleic acid (ctDNA)/cfDNA analysis, multi-omics integration, and dynamic imaging are enabling longitudinal monitoring of tumor state transitions and may facilitate identification of transient biological states preceding stable resistance. Integrating temporal tumor biology with therapeutic sequencing strategies, adaptive treatment schedules, and biomarker-guided monitoring may therefore help test whether specific adaptive states can be therapeutically exploited and may refine precision oncology approaches.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"7 ","pages":"1002390"},"PeriodicalIF":0.0,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13424807/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148655189","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}
引用次数: 0
Distinct transcriptomic features of tumor and stromal cells in direct contact in luminal and triple-negative breast cancers. 乳腺癌和三阴性乳腺癌中直接接触的肿瘤和基质细胞的转录组学特征。
Exploration of targeted anti-tumor therapy Pub Date : 2026-07-29 eCollection Date: 2026-01-01 DOI: 10.37349/etat.2026.1002388
Anna Yu Kalinchuk, Ivan A Patskan, Evgeniya S Grigorieva, Liubov A Tashireva
{"title":"Distinct transcriptomic features of tumor and stromal cells in direct contact in luminal and triple-negative breast cancers.","authors":"Anna Yu Kalinchuk, Ivan A Patskan, Evgeniya S Grigorieva, Liubov A Tashireva","doi":"10.37349/etat.2026.1002388","DOIUrl":"10.37349/etat.2026.1002388","url":null,"abstract":"<p><strong>Aim: </strong>The aim was to determine the transcriptomic features of tumor and stromal cells in direct contact within tumor nodules in luminal and triple-negative breast cancer.</p><p><strong>Methods: </strong>Spatial transcriptomic profiling was performed using the Visium 10x platform on FFPE tumor tissue sections from 10 patients with luminal breast cancer and 9 patients with triple-negative breast cancer. Manual morphological annotation of spots and evaluation of differentially expressed genes (DEGs) in identified spot clusters were performed using Loupe Browser v8.0.0 (10X Genomics, USA). Activated biological processes were assessed using the Enrichr online resource and the GO Biological Process 2025 database. Ligand-receptor pairs were identified using the CellChat package (v2.0) in R (v4.4.2).</p><p><strong>Results: </strong>In luminal breast cancer, mixed cluster (tumor cells colocalized with stromal cells) was characterized by overexpression of genes encoding S100A family Ca<sup>2+</sup>-binding proteins (<i>S100A4</i>, <i>S100A8</i>, <i>S100A9</i>), matrix metalloproteinases (<i>MMP2</i>, <i>MMP7</i>, <i>MMP14</i>), cytokeratins (<i>KRT5</i>, <i>KRT7</i>, <i>KRT15</i>, <i>KRT23, KRT81</i>), the mesenchymal marker <i>VIM</i>, and epithelial-mesenchymal transition (EMT)-associated genes (<i>ICAM1</i>, <i>PRRX1</i>) compared to tumor-only cluster. In triple-negative breast cancer, mixed cluster showed overexpression of <i>S100A2</i>, <i>S100A8</i>, <i>S100A9</i>, the epithelial gene <i>KRT6B</i>, the cancer stem cell marker <i>CD44</i>, and <i>NOTCH2</i>, which is associated with negative regulation of EMT. In both breast cancer subtypes, mixed cluster showed transcriptomic enrichment of gene sets associated with regulation of the ERK/MAPK cascade, apoptosis, and cell adhesion and migration. Ligand-receptor pairs associated with cell-cell contact, EMT, and immune response were also detected in colocalized cells, with a broader spectrum of these pairs observed in luminal breast cancer.</p><p><strong>Conclusions: </strong>This study assessed the transcriptomic characteristics of directly contacting tumor and stromal cells and identified the spectrum of ligand-receptor pairs mediating their interactions. Characterizing the properties of cells at the tumor-stroma interface helps unravel mechanisms of breast cancer progression and identify novel diagnostic markers and therapeutic targets.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"7 ","pages":"1002388"},"PeriodicalIF":0.0,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13424803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148655119","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}
引用次数: 0
Comparative outcomes of open, laparoscopic, and robot-assisted radical cystectomy using IPTW-adjusted trifecta and pentafecta metrics. 使用iptw调整的三直肠和五直肠指标进行开放、腹腔镜和机器人辅助根治性膀胱切除术的比较结果。
Exploration of targeted anti-tumor therapy Pub Date : 2026-07-29 eCollection Date: 2026-01-01 DOI: 10.37349/etat.2026.1002389
Nobutaka Nishimura, Makito Miyake, Yuki Oda, Takuto Shimizu, Kota Iida, Mitsuru Tomizawa, Kenta Onishi, Shunta Hori, Yosuke Morizawa, Daisuke Gotoh, Yasushi Nakai, Nobumichi Tanaka
{"title":"Comparative outcomes of open, laparoscopic, and robot-assisted radical cystectomy using IPTW-adjusted trifecta and pentafecta metrics.","authors":"Nobutaka Nishimura, Makito Miyake, Yuki Oda, Takuto Shimizu, Kota Iida, Mitsuru Tomizawa, Kenta Onishi, Shunta Hori, Yosuke Morizawa, Daisuke Gotoh, Yasushi Nakai, Nobumichi Tanaka","doi":"10.37349/etat.2026.1002389","DOIUrl":"10.37349/etat.2026.1002389","url":null,"abstract":"<p><strong>Aim: </strong>Minimally invasive approaches for radical cystectomy (RC) have been increasingly adopted; however, comparative evidence regarding surgical quality and perioperative outcomes among open (ORC), laparoscopic (LRC), and robot-assisted RC (RARC) remains limited. This study evaluated these three modalities using standardized composite metrics, trifecta and pentafecta, and inverse probability of treatment weighting.</p><p><strong>Methods: </strong>We retrospectively analyzed 192 patients who underwent RC with ileal conduit or neobladder reconstruction between 2006 and 2023. Inverse probability of treatment weighting was applied using comprehensive clinicopathological covariates. Trifecta and pentafecta achievements, perioperative parameters, and postoperative complications were compared among the ORC (<i>n</i> = 110), LRC (<i>n</i> = 38), and RARC (<i>n</i> = 44) groups.</p><p><strong>Results: </strong>RARC achieved the most favorable perioperative and surgical outcomes. Specifically, RARC showed significantly higher rates of several trifecta and pentafecta components than ORC, including fewer positive soft tissue surgical margins (0.0% vs. 5.2%, <i>P</i> < 0.01), reduced major complication rates within 90 days (16.1% vs. 44%, <i>P</i> < 0.05), and fewer urinary diversion-related sequelae within 12 months (1.5% vs. 13.5%, <i>P</i> < 0.05). RARC was also associated with significantly lower blood loss than ORC (380 ± 513 mL vs. 2,913 ± 2,997 mL, <i>P</i> < 0.01), as well as lower rates of pelvic abscess, gastrointestinal anastomotic leakage, and obstructive ileus (all <i>P</i> < 0.01) than ORC. In contrast, LRC was not superior to ORC in terms of major complications or diversion-related outcomes. Local pelvic recurrence within 12 months did not differ significantly among the three modalities.</p><p><strong>Conclusions: </strong>RARC may be a favorable surgical option for reducing perioperative morbidity in patients with high-grade bladder cancer, with comparable 12-month local recurrence rates among surgical approaches.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"7 ","pages":"1002389"},"PeriodicalIF":0.0,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13424797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148655155","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}
引用次数: 0
Paclitaxel and carboplatin after disease progression on immune checkpoint inhibitor for patients with metastatic urothelial carcinoma. 转移性尿路上皮癌患者的免疫检查点抑制剂治疗进展后紫杉醇和卡铂。
Exploration of targeted anti-tumor therapy Pub Date : 2026-07-29 eCollection Date: 2026-01-01 DOI: 10.37349/etat.2026.1002387
Albert Jang, Miguel Muniz, Megan Spychalla, Timothy Burns, Amrit Singh, Elisabeth I Heath, Brian A Costello, Jacob J Orme, J Fernando Quevedo, Daniel S Childs, Lance C Pagliaro
{"title":"Paclitaxel and carboplatin after disease progression on immune checkpoint inhibitor for patients with metastatic urothelial carcinoma.","authors":"Albert Jang, Miguel Muniz, Megan Spychalla, Timothy Burns, Amrit Singh, Elisabeth I Heath, Brian A Costello, Jacob J Orme, J Fernando Quevedo, Daniel S Childs, Lance C Pagliaro","doi":"10.37349/etat.2026.1002387","DOIUrl":"10.37349/etat.2026.1002387","url":null,"abstract":"<p><strong>Aim: </strong>Despite advances with immune checkpoint inhibitor (ICI)-based regimens in the past decade, patients with metastatic urothelial cancer (mUC) face a poor prognosis with few approved options. Platinum-based chemotherapy with paclitaxel and carboplatin (TC) +/- ICI may be a feasible choice.</p><p><strong>Methods: </strong>We generated an IRB-approved, HIPAA-compliant retrospective database of patients at Mayo Clinic Cancer Center with mUC who started TC +/- ICI after disease progression on ICI from January 2018 through December 2024. Baseline demographics, clinicopathologic features, and treatment outcomes were extracted from the electronic health record. Kaplan-Meier method was used to calculate median duration of response (DOR), progression-free survival (PFS) and overall survival (OS).</p><p><strong>Results: </strong>There were 32 patients who fit inclusion criteria, including 31 patients who had disease progression on ICI in the metastatic setting and 1 patient who developed metastatic disease on adjuvant nivolumab. Patients received a median of 4 cycles (range 1-14) of TC over median 12 weeks (range 3-53). Overall, 81% of patients received TC concurrently with an ICI, and 28% continued maintenance ICI after TC discontinuation (at the treating oncologist's discretion due to adequate response or toxicity). The best objective response rate was 41% and disease control rate was 75%, with median DOR of 4.8 months (IQR 2.7-10.4), median PFS of 4.6 months (IQR 3.3-10.2), and median OS of 9.4 months (IQR 6.3-15.9). Some patients in this series had very durable responses with PFS > 12 months and OS > 24 months. TC +/- ICI was overall well tolerated with expected type and severity of adverse events.</p><p><strong>Conclusions: </strong>Strategies to overcome ICI resistance are needed, and TC +/- ICI after disease progression on an ICI shows promising tolerability and efficacy in this setting for patients with mUC. Our series was notable for some patients having a durable response. Validation in larger cohorts is warranted.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"7 ","pages":"1002387"},"PeriodicalIF":0.0,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13424796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148655186","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}
引用次数: 0
FGFR3 gene alteration and protein expression in upper urinary tract carcinoma: unsuitability of ureteroscopic biopsy specimens for FGFR3 RNA testing. 上尿路癌中FGFR3基因改变和蛋白表达:输尿管镜活检标本不适合FGFR3 RNA检测
Exploration of targeted anti-tumor therapy Pub Date : 2026-07-28 eCollection Date: 2026-01-01 DOI: 10.37349/etat.2026.1002385
Makito Miyake, Yuki Oda, Nobutaka Nishimura, Sayuri Ohnishi, Kazuki Miyazaki, Takuto Shimizu, Takuya Owari, Kota Iida, Kiyohide Fujimoto
{"title":"<i>FGFR3</i> gene alteration and protein expression in upper urinary tract carcinoma: unsuitability of ureteroscopic biopsy specimens for <i>FGFR3</i> RNA testing.","authors":"Makito Miyake, Yuki Oda, Nobutaka Nishimura, Sayuri Ohnishi, Kazuki Miyazaki, Takuto Shimizu, Takuya Owari, Kota Iida, Kiyohide Fujimoto","doi":"10.37349/etat.2026.1002385","DOIUrl":"10.37349/etat.2026.1002385","url":null,"abstract":"<p><p>We aimed to evaluate the suitability of archival ureteroscopic (URS) biopsy specimens for fibroblast growth factor receptor 3 (<i>FGFR3</i>) biomarker analysis in upper urinary tract urothelial carcinoma. Thirty-six patients with upper urinary tract urothelial carcinoma who underwent diagnostic URS and radical nephroureterectomy (RNU) were included. Among the 36 RNU-derived tissue specimens, 33 (92%) yielded valid <i>FGFR3</i> RNA test results; the remaining three (8.3%) showed test failure because of undetectable amplification by reverse transcriptase-polymerase chain reaction. Of the 33 RNU specimens with valid amplification, eight (24%) had <i>FGFR3</i> alterations. Of these eight specimens, two (25%) were valid for <i>FGFR3</i> RNA testing; one showed positive concordance with the paired RNU specimen, whereas the other did not. The remaining six specimens (75%) showed test failure. Correlation analysis of FGFR3 immunohistochemical staining scores demonstrated a moderate positive correlation between RNU and paired URS specimens (Spearman's ρ = 0.47, <i>P</i> = 0.004). Our findings indicate that URS biopsy specimens are unsuitable for <i>FGFR3</i> RNA testing but may be useful for protein-based biomarker analysis when RNU specimens are unavailable.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"7 ","pages":"1002385"},"PeriodicalIF":0.0,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13424798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148655122","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}
引用次数: 0
Transurethral laser ablation using 980-nm diode laser for recurrent non-muscle invasive bladder cancer. 经尿道980纳米二极管激光消融治疗复发性非肌性浸润性膀胱癌。
Exploration of targeted anti-tumor therapy Pub Date : 2026-07-28 eCollection Date: 2026-01-01 DOI: 10.37349/etat.2026.1002386
Hideo Fukuhara, Syo Shimasaki, Erika Yamashita, Yoshitaka Kurano, Kaya Atagi, Ryu Shigehisa, Daigo Takemori, Shinkuro Yamamoto, Hiroto Osakabe, Tomoya Nao, Tsutomu Shimamoto, Satoshi Fukata, Shingo Ashida, Keiji Inoue
{"title":"Transurethral laser ablation using 980-nm diode laser for recurrent non-muscle invasive bladder cancer.","authors":"Hideo Fukuhara, Syo Shimasaki, Erika Yamashita, Yoshitaka Kurano, Kaya Atagi, Ryu Shigehisa, Daigo Takemori, Shinkuro Yamamoto, Hiroto Osakabe, Tomoya Nao, Tsutomu Shimamoto, Satoshi Fukata, Shingo Ashida, Keiji Inoue","doi":"10.37349/etat.2026.1002386","DOIUrl":"10.37349/etat.2026.1002386","url":null,"abstract":"<p><strong>Aim: </strong>Transurethral laser ablation (TULA) for recurrent bladder cancer is a less invasive treatment method for patients. We report here our initial clinical experience with TULA for recurrent bladder cancer.</p><p><strong>Methods: </strong>This retrospective study analyzed 48 patients. Twenty-four cases were treated with TULA and another 24 cases were treated with transurethral resection of bladder tumor (TURBT) from Feb 2024 to Mar 2025 at Kochi Medical School Hospital. Intraoperative and postoperative outcomes and recurrence-free survival (RFS) were analyzed between TULA and TURBT.</p><p><strong>Results: </strong>This study showed that TULA using a 980-nm diode laser was significantly shorter than TURBT in terms of perioperative results: operative time, hospital stay, catheterization, bladder irrigation, and postoperative hospital stay. Regarding the occurrence of complications, TULA was observed to be less prevalent than TURBT in all cases. Kaplan-Meier curves showed that TULA was significantly associated with longer RFS compared to TURBT (hazard ratio 4.739; 95% confidence interval, 1.272-17.65; <i>p</i> = 0.02039).</p><p><strong>Conclusions: </strong>Our preliminary results showed that TULA for recurrent bladder cancer is feasible and safe.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"7 ","pages":"1002386"},"PeriodicalIF":0.0,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13424799/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148655141","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}
引用次数: 0
Mechanistic study of antisense long non-coding RNA STEAP3-AS1 in breast cancer. 反义长链非编码RNA STEAP3-AS1在乳腺癌中的作用机制研究。
Exploration of targeted anti-tumor therapy Pub Date : 2026-07-23 eCollection Date: 2026-01-01 DOI: 10.37349/etat.2026.1002380
Jinquan Sun, Jiayong Cui, Tianlei Qiu, Guoshuang Shen
{"title":"Mechanistic study of antisense long non-coding RNA <i>STEAP3-AS1</i> in breast cancer.","authors":"Jinquan Sun, Jiayong Cui, Tianlei Qiu, Guoshuang Shen","doi":"10.37349/etat.2026.1002380","DOIUrl":"10.37349/etat.2026.1002380","url":null,"abstract":"<p><strong>Aim: </strong>This study aims to investigate the expression and function of antisense long non-coding RNA (lncRNA) <i>STEAP3-AS1</i> in breast cancer (BC). Additionally, it explores STEAP3's regulatory relationship with <i>STEAP3-AS1</i> and potential signaling pathways to provide a theoretical foundation for identifying novel therapeutic targets.</p><p><strong>Methods: </strong>Database prediction and collection of tissue samples were employed alongside a cell proliferation assay and Transwell migration and invasion assay to examine <i>STEAP3-AS1</i> expression levels in BC tissues and cell lines, as well as its impact on cellular functions. Statistical analyses were performed, including two-tailed Student's <i>t</i>-test, Mann-Whitney <i>U</i> test and analysis of variance (ANOVA).</p><p><strong>Results: </strong>Both database and 9 paired clinical tissue sample results demonstrate that <i>STEAP3-AS1</i> expression was significantly downregulated in BC compared with normal breast tissues (<i>P</i> < 0.05). Compared with the estrogen receptor/progesterone receptor (ERPR)-negative (-)/human epidermal growth factor receptor-2 (Her2)-positive (+) subtype, the ERPR(+)/Her2(-) and ERPR(-)/Her2(-) subtypes exhibited a significantly lower expression level of <i>STEAP3-AS1</i> (<i>P</i> < 0.05). Overexpression of <i>STEAP3-AS1</i> markedly suppressed the proliferation, migration, and invasion capabilities of MDA-MB-231 and MCF-7 cells compared with negative controls (<i>P</i> < 0.05). Furthermore, <i>STEAP3-AS1</i> exhibited a positive synergistic effect with its sense strand STEAP3, inhibiting BC cell migration and invasion.</p><p><strong>Conclusions: </strong>This study is the first to demonstrate the tumor-suppressive role of <i>STEAP3-AS1</i> in BC. These findings provide novel insights into the mechanisms underlying BC progression and offer critical theoretical support for the development of new therapeutic strategies.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"7 ","pages":"1002380"},"PeriodicalIF":0.0,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13392826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148581363","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}
引用次数: 0
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