Oncotarget最新文献

{"title":"Optimizing enfortumab vedotin plus pembrolizumab therapy.","authors":"Elias Antoine Karam, Yaghi César Céline, Gilles Prince, Fouad Attieh, Hampig Raphael Kourie, Joseph Kattan, Elie Nemer","doi":"10.18632/oncotarget.28741","DOIUrl":"10.18632/oncotarget.28741","url":null,"abstract":"<p><p>Often associated with a poor prognosis, advanced urothelial carcinoma (aUC) has progressed to muscle-invasive or metastatic stages. Traditionally, chemotherapy has been the primary treatment for aUC, though its effectiveness in advanced stages remains limited. Recent developments have introduced promising therapies, notably the combination of enfortumab vedotin with pembrolizumab, which is now recommended as the first-line therapy following the EV-302 trial results. This combination has demonstrated significant improvements in survival rates. This review aims to explore the evolution of treatment strategies for aUC, emphasizing the shift towards immunotherapy and targeted therapies, and discusses the potential for optimized treatment algorithms to improve patient outcomes.</p>","PeriodicalId":19499,"journal":{"name":"Oncotarget","volume":"16 ","pages":"481-494"},"PeriodicalIF":0.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12173200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317550","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":"Molecular landscape of HER2-mutated non-small cell lung cancer in Northeastern Brazil: Clinical, histopathological, and genomic insights.","authors":"Cleto Dantas Nogueira, Samuel Frota, Huylmer Lucena Chaves, Juliana Cordeiro de Sousa, Guilherme de Sousa Veloso, Francisco Jonathan Dos Santos Araujo, Gabriel Barbosa Silva, Samuel Silva Ferreira, Marclesson Santos Alves, Fabio Nasser, Ezequiel Rangel, Francisco Martins Neto, Iusta Caminha, Ellen Nascimento, Fabio Tavora","doi":"10.18632/oncotarget.28737","DOIUrl":"10.18632/oncotarget.28737","url":null,"abstract":"<p><p>HER2 genomic alterations characterize a specific subset of NSCLC with potential therapeutic relevance. While most studies focus on populations from high-income countries, data from Latin America remains scarce. We retrospectively analyzed 13 HER2-mutated NSCLC cases from a single institution in Northeastern Brazil, integrating clinical, histopathological, immunohistochemical, and molecular findings. Predominant histological patterns included acinar and lepidic subtypes, with HER2 mutations primarily involving exon 20 insertions (A775_G776insYVMA) and frequent co-alterations in TP53, KRAS, and STK11. HER2 protein expression assessed by IHC showed low scores (0-2+) in most cases, while HER2 gene amplification was confirmed in one case by D-DISH and NGS. Tumor mutation burden was universally low. Treatment responses varied, with one patient receiving trastuzumab deruxtecan. Our findings highlight the molecular diversity and diagnostic challenges of HER2-mutated NSCLC in underrepresented populations, emphasizing the need for comprehensive molecular profiling and expanded access to targeted therapies.</p>","PeriodicalId":19499,"journal":{"name":"Oncotarget","volume":"16 ","pages":"467-479"},"PeriodicalIF":0.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12173199/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317549","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":"Retraction: ARHGAP24 inhibits cell cycle progression, induces apoptosis and suppresses invasion in renal cell carcinoma.","authors":"Gaosi Xu, Xiongbing Lu, Tianlun Huang, Jie Fan","doi":"10.18632/oncotarget.28749","DOIUrl":"10.18632/oncotarget.28749","url":null,"abstract":"","PeriodicalId":19499,"journal":{"name":"Oncotarget","volume":"16 ","pages":"480"},"PeriodicalIF":0.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12173197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317551","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":"Genetic characteristics of blastic plasmacytoid dendritic cell neoplasm: A single institution experience.","authors":"Fei Fei, Milhan Telatar, Vanina Tomasian, Lisa Chang, Olga Danilova, Javier Arias-Stella, Raju Pillai, Lorinda Soma, Parastou Tizro, Pamela S Becker, Anthony S Stein, Guido Marcucci, Michelle Afkhami","doi":"10.18632/oncotarget.28742","DOIUrl":"10.18632/oncotarget.28742","url":null,"abstract":"<p><p>Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy with poorly characterized molecular features. To identify disease-specific mutational profiles, we performed targeted next-generation sequencing (NGS) on a cohort of 21 BPDCN patients. Our study revealed that <i>TET2</i> (57%) and <i>ASXL1</i> (33%) were the most frequently mutated genes, followed by <i>NRAS</i> (29%), <i>SRSF2</i> (14%), <i>ZRSR2</i> (14%), and <i>KMT2D</i> (14%). Further analysis demonstrated that poor prognosis was associated with older age (≥65 years), the presence of three or more mutations, <i>TET2</i> mutations, <i>TET2</i> truncating mutations, and mutations involving DNA methylation pathways. In contrast, patients who underwent hematopoietic stem cell transplantation (HSCT) exhibited more favorable clinical outcomes. Moreover, our study indicated that <i>CCDC50</i> expression was significantly elevated in BPDCN cases compared to those with acute myeloid leukemia (AML) or chronic monomyelocytic leukemia (CMML), suggesting that <i>CCDC50</i> may serve as a reliable diagnostic marker for distinguishing BPDCN from AML, as well as a potential biomarker for disease monitoring. Finally, our investigation of mutational profiles in sequentially paired specimens revealed a high prevalence of bone marrow clonal hematopoiesis in patients with BPDCN. In conclusion, the genetic landscape of BPDCN identified in this study provides valuable insights that may improve diagnostic accuracy and guide prognostic evaluation and therapeutic strategies. However, validation in larger, independent cohorts are warranted.</p>","PeriodicalId":19499,"journal":{"name":"Oncotarget","volume":"16 ","pages":"495-507"},"PeriodicalIF":0.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12173198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317548","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":"Case Report WIN-MTB-2023001 WIN International Molecular Tumor Board A 62-year-old male with metastatic colorectal cancer with 5 prior lines of treatment.","authors":"Alberto Hernando-Calvo, Razelle Kurzrock, Nadia Saoudi Gonzalez, Shai Magidi, Catherine Bresson, Fanny Wunder, Giulia Pretelli, Agatha Martin Casado, Wafik S El-Deiry","doi":"10.18632/oncotarget.28744","DOIUrl":"10.18632/oncotarget.28744","url":null,"abstract":"<p><p>Heavily pretreated metastatic colorectal cancer (mCRC) poses significant therapeutic challenges. Advances in molecular profiling enables personalized strategies. We present a 62-year-old male with mCRC harboring <i>BRAF</i>, <i>MET</i>, <i>APC</i>, <i>TP53</i> and <i>NRAS</i> alterations, following FOLFOX and FOLFIRI, dabrafenib plus panitumumab, and a BRAF inhibitor clinical trial, each leading to initial responses followed by disease progression. WIN Consortium International Molecular Tumor Board (MTB), included experts from institutions across 13 countries. Enrollment in suitable clinical trials was explored but limited by availability. Personalized combinations suggested included amivantamab-vmjw (anti-MET/EGFR antibody) (one-third standard dose) (for MET amplification and due to prior response to anti-EGFR antibody), trametinib, 1 mg po daily (MEK inhibitor for <i>BRAF V600E</i> mutation), and regorafenib (may have WNT inhibitor activity relevant to <i>APC</i> mutation; VEGFR activity relevant since <i>TP53</i> alterations upregulate VEGF/VEGFR axis) starting at 40 mg po daily three weeks on, one week off. Another option was trametinib at 1 mg daily, cetuximab (EGFR antibody), 250 mg/m² IV every two-weeks, and cabozantinib (MET and VEGFR inhibitor), 40 mg po daily. FOLFOXFIRI combined with bevacizumab, or liver-directed therapies for hepatic metastases, or regorafenib with 5FU, or crizotinib (MET inhibitor) combined with regorafenib or dabrafenib, was also suggested. This case emphasizes the critical role of comprehensive molecular profiling and personalized therapeutic approaches in managing complex mCRC. The WIN International MTB aims to provide treatment and biomarker analysis discussion with the ultimate goal of optimizing treatment efficacy by targeting specific molecular alterations, though final treatment decisions remain at the discretion of the treating physician.</p>","PeriodicalId":19499,"journal":{"name":"Oncotarget","volume":"16 ","pages":"456-466"},"PeriodicalIF":0.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12175699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317547","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":"Retraction: MicroRNA-564 is downregulated in glioblastoma and inhibited proliferation and invasion of glioblastoma cells by targeting TGF-β1.","authors":"Chunming Jiang, Fang Shen, Jianmin Du, Zhaoyang Hu, Xiaoli Li, Jin Su, Xiaohua Wang, Xianmei Huang","doi":"10.18632/oncotarget.28748","DOIUrl":"10.18632/oncotarget.28748","url":null,"abstract":"","PeriodicalId":19499,"journal":{"name":"Oncotarget","volume":"16 ","pages":"454-455"},"PeriodicalIF":0.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12173196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317552","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":"Beyond DNA damage response: Immunomodulatory attributes of CHEK2 in solid tumors.","authors":"Helen Qian, Heba Ali, Vivekanudeep Karri, Justin T Low, David M Ashley, Amy B Heimberger, Lucy A Godley, Adam M Sonabend, Crismita Dmello","doi":"10.18632/oncotarget.28740","DOIUrl":"10.18632/oncotarget.28740","url":null,"abstract":"<p><p>The <i>CHEK2</i> gene serves a canonical role in the DNA damage response (DDR) pathway encoding the regulatory kinase CHK2 in the homologous recombination (HR) repair of double-strand breaks (DSB). Although <i>CHEK2</i> is traditionally considered a tumor suppressor gene, recent studies suggest additional functions. Across several cohort studies, <i>CHEK2</i> expression was negatively correlated with the efficacy of immune checkpoint inhibitors (ICI), which target the interaction between effector immune and tumor cells. This review explores two possible explanations for this observed phenomenon: the first relating to the canonical role of <i>CHEK2</i>, and the second introducing a novel role of the <i>CHEK2</i> gene in immunomodulation of the tumor microenvironment (TME). DDR mutations have been implicated in increased levels of tumor mutation burden (TMB), often manifesting as neoepitope expression on the tumor cell surface recognized by effector immune cells. As a result, impaired DNA repair due to <i>CHEK2</i> loss of function, either from germline deleterious variants or acquired mutations, results in the recruitment of CD8+ cytotoxic T-cells and subsequent efficacy of ICI treatment. However, functional loss of <i>CHEK2</i> may be directly involved in potentiating the immune response through canonical inflammatory and anti-tumor pathways, acting through the cGAS-STING pathway. Although the exact mechanism by which <i>CHEK2</i> modulates immune responses is still under investigation, combination therapy with CHEK1/2 inhibition and ICI immunotherapy has shown benefit in preclinical studies of several solid tumors.</p>","PeriodicalId":19499,"journal":{"name":"Oncotarget","volume":"16 ","pages":"445-453"},"PeriodicalIF":0.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12151402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258646","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":"Correction: Overcoming melanoma resistance to vemurafenib by targeting CCL2-induced miR-34a, miR-100 and miR-125b.","authors":"Elisabetta Vergani, Lorenza Di Guardo, Matteo Dugo, Sara Rigoletto, Gabrina Tragni, Roberta Ruggeri, Federica Perrone, Elena Tamborini, Annunziata Gloghini, Flavio Arienti, Barbara Vergani, Paola Deho, Loris De Cecco, Viviana Vallacchi, Paola Frati, Eriomina Shahaj, Antonello Villa, Mario Santinami, Filippo De Braud, Licia Rivoltini, Monica Rodolfo","doi":"10.18632/oncotarget.28746","DOIUrl":"10.18632/oncotarget.28746","url":null,"abstract":"","PeriodicalId":19499,"journal":{"name":"Oncotarget","volume":"16 ","pages":"443-444"},"PeriodicalIF":0.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12151401/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258647","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":"Exceptional responders to immunotherapy in pancreatic cancer: A multi-institutional case series of a rare occurrence.","authors":"Kavin Sugumar, Andrew Alabd, Andre Alabd, Jonathan J Hue, Josh Lyons, Sherri Fields, Zev Wainberg, Lei Zheng, Brianna Coogle, Anup Kasi, Nicholas Grewal, Hedy L Kindler, Jason Starr, Ashwin R Sama, Jordan M Winter","doi":"10.18632/oncotarget.28739","DOIUrl":"10.18632/oncotarget.28739","url":null,"abstract":"<p><strong>Introduction: </strong>Immunotherapy has emerged as a standard treatment option for multiple solid tumors. However, most patients with pancreatic cancer (PC) do not derive a significant benefit. Identification and analyses of exceptional responders could eventually offer hints as to why PC is resistant to immunotherapy.</p><p><strong>Methods: </strong>Oncologists from cancer centers in the United States were contacted to identify patients with PC who responded to immunotherapy. Exceptional responders were defined as those having either partial (PR) or complete response (CR) based on Response Evaluation Criteria in Solid Tumors, or biochemical response (CA 19-9 levels) after starting immunotherapy. Patients receiving concurrent chemotherapy were excluded.</p><p><strong>Results: </strong>14 patients met inclusion criteria. Immunotherapy drugs included checkpoint inhibitors and macrophage inhibitors. Eight patients (42%) were MSI (microsatellite instability)-high. Radiologically, 82% had PR. Four patients (28%) had marked reduction in CA 19-9. The median progression-free survival was 12 months from the start of immunotherapy. Median survival was not reached. The 1- and 2-year survival probabilities were 80%, 70% respectively.</p><p><strong>Conclusion: </strong>Majority of clinical trials evaluating immunotherapy in PC have yielded disappointing response rates compared to other solid tumors. Our case series adds to published data from early-phase trials supporting the promise of immunotherapy in some patients with PC.</p>","PeriodicalId":19499,"journal":{"name":"Oncotarget","volume":"16 ","pages":"427-442"},"PeriodicalIF":0.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12151408/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258649","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":"Correction: Rapamycin inhibits mSin1 phosphorylation independently of mTORC1 and mTORC2.","authors":"Yan Luo, Lei Liu, Yang Wu, Karnika Singh, Bing Su, Nan Zhang, Xiaowei Liu, Yangmei Shen, Shile Huang","doi":"10.18632/oncotarget.28745","DOIUrl":"10.18632/oncotarget.28745","url":null,"abstract":"","PeriodicalId":19499,"journal":{"name":"Oncotarget","volume":"16 ","pages":"425-426"},"PeriodicalIF":0.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12151400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258648","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}