Oncotarget最新文献_第2页

Retraction: Nestin suppression attenuates invasive potential of endometrial cancer cells by downregulating TGF-β signaling pathway. 缩回：抑制Nestin通过下调TGF-β信号通路减弱子宫内膜癌细胞的侵袭潜能。

Oncotarget Pub Date : 2025-08-19 DOI: 10.18632/oncotarget.28763

Amber A Bokhari, Tabari M Baker, Batsukh Dorjbal, Sana Waheed, Christopher M Zahn, Chad A Hamilton, G Larry Maxwell, Viqar Syed

引用次数: 0

Clinical and analytical validation of MI Cancer Seek®, a companion diagnostic whole exome and whole transcriptome sequencing-based comprehensive molecular profiling assay. MI Cancer Seek®的临床和分析验证，这是一种基于全外显子组和全转录组测序的综合分子分析方法。

Oncotarget Pub Date : 2025-08-13 DOI: 10.18632/oncotarget.28761

Valeriy Domenyuk, Kasey Benson, Peggy Carter, Daniel Magee, Jian Zhang, Nitin Bhardwaj, Hongseok Tae, James Wacker, Foram Rathi, Siobhan Miick, Aastha Kohli, Joshua Carroll, Lori Cuyugan, Evelyn Perez, Wayeesha Zhang, John Collins, Patrick Kennedy, Jeremy Ellis, Adam Stark, Andrey Loskutov, Brittany Cuttone, Blake Taylor, Rebecca Feldman, Jeff Swenson, David Bryant, Robert Hahn-Lowry, Raunaq Kaushal, Jennifer R Ribeiro, Jim Abraham, Milan Radovich, George W Sledge, Matthew Oberley, David Spetzler

{"title":"Clinical and analytical validation of MI Cancer Seek®, a companion diagnostic whole exome and whole transcriptome sequencing-based comprehensive molecular profiling assay.","authors":"Valeriy Domenyuk, Kasey Benson, Peggy Carter, Daniel Magee, Jian Zhang, Nitin Bhardwaj, Hongseok Tae, James Wacker, Foram Rathi, Siobhan Miick, Aastha Kohli, Joshua Carroll, Lori Cuyugan, Evelyn Perez, Wayeesha Zhang, John Collins, Patrick Kennedy, Jeremy Ellis, Adam Stark, Andrey Loskutov, Brittany Cuttone, Blake Taylor, Rebecca Feldman, Jeff Swenson, David Bryant, Robert Hahn-Lowry, Raunaq Kaushal, Jennifer R Ribeiro, Jim Abraham, Milan Radovich, George W Sledge, Matthew Oberley, David Spetzler","doi":"10.18632/oncotarget.28761","DOIUrl":"10.18632/oncotarget.28761","url":null,"abstract":"The precision oncology industry has evolved rapidly within the past two decades, although treatment selection remains a complex undertaking. Access to timely, accurate, and comprehensive molecular profiling data is imperative to improving patient outcomes within the expanding sphere of Food and Drug Administration (FDA)-approved targeted therapies. Caris Life Sciences has developed MI Cancer Seek®, an FDA-approved whole exome and whole transcriptome sequencing-based molecular test encompassing adult and pediatric tumor profiling, eight companion diagnostics (CDx), and additional laboratory developed test (LDT) capabilities. Patient tissue is maximized through simultaneous analysis of DNA and RNA with minimum input of 50 ng. The clinical and analytical validation presented herein demonstrates non-inferiority of MI Cancer Seek relative to other FDA-approved CDx tests (>97% negative and positive percent agreement), as well as its precision, sensitivity, and specificity. Accordingly, MI Cancer Seek represents a safe and effective comprehensive molecular test option supporting biomarker-directed care for oncology patients.","PeriodicalId":19499,"journal":{"name":"Oncotarget","volume":"16 ","pages":"642-659"},"PeriodicalIF":0.0,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144848202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

PCAIs stimulate MAPK, PI3K/AKT pathways and ROS-Mediated apoptosis in aromatase inhibitor-resistant breast cancer cells while disrupting actin filaments and focal adhesion. PCAIs刺激芳香酶抑制剂耐药乳腺癌细胞中MAPK、PI3K/AKT通路和ros介导的凋亡，同时破坏肌动蛋白丝和局灶粘附。

Oncotarget Pub Date : 2025-07-29 DOI: 10.18632/oncotarget.28759

Jassy Mary S Lazarte, Kweku Ofosu-Asante, Syreeta L Tilghman, Nazarius S Lamango

{"title":"PCAIs stimulate MAPK, PI3K/AKT pathways and ROS-Mediated apoptosis in aromatase inhibitor-resistant breast cancer cells while disrupting actin filaments and focal adhesion.","authors":"Jassy Mary S Lazarte, Kweku Ofosu-Asante, Syreeta L Tilghman, Nazarius S Lamango","doi":"10.18632/oncotarget.28759","DOIUrl":"10.18632/oncotarget.28759","url":null,"abstract":"The estrogen receptor is overexpressed in and promotes 67-80% and 90% of female and male breast cancer cases, respectively. Hormone independence, enhanced motility, and signaling by growth factors have been attributed to aromatase inhibitor (AI) resistance and MAPK pathway activation. We used long-term letrozole-treated (LTLT-Ca) breast cancer cells to evaluate polyisoprenylated cysteinyl amide inhibitors (PCAIs) as potential therapies for AI-resistant breast cancer. PCAIs specifically disrupt G-proteins such as KRAS, an upstream regulator of MAPK and PI3K/AKT pathways. PCAIs were tested against the viability, phosphorylation of MAPK and PI3K/AKT pathways, apoptosis, and migration of LTLT-Ca cells. NSL-YHJ-2-27 was potent against LTLT-Ca viability with an EC50 of 4.8 μM. MEK (p-MEK1/2), ERK (p-ERK1/2), and p90RSK (p-p90RSK) phosphorylation were significantly increased by 2-, 2-, and 6.4-fold, respectively. PCAIs increased AKT phosphorylation 36-fold. NSL-YHJ-2-27 at 2, 3 and 5 μM stimulated ROS generation by 4-, 8- and 10-fold, respectively. PCAIs inhibited cell proliferation and colony formation by 95% and 74%, respectively, increased active caspase 7 and BAX 1.5-fold and 56%, respectively. NSL-YHJ-2-27 (10 μM) induced LTLT-Ca spheroid degeneration by 61%. LTLT-Ca cell migration was inhibited by 31 and 80% following treatment with 2 and 5 μM NSL-YHJ-2-27, respectively. NSL-YHJ-2-27 disrupted F-actin filaments, vinculin punctates and levels by 33%. These results indicate that the PCAIs' activation of the MAPK and PI3K/AKT pathways causes apoptosis, possibly through proapoptotic p-p90RSK isoforms, AKT-induced ROS production or anoikis through disruption of focal adhesion. These effects against LTLT-Ca cells suggest potential PCAIs therapeutic applications against antihormonal-resistant breast cancers.","PeriodicalId":19499,"journal":{"name":"Oncotarget","volume":"16 ","pages":"621-641"},"PeriodicalIF":0.0,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12309409/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144743501","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

Dissecting the functional differences and clinical features of R-spondin family members in metastatic prostate cancer. 转移性前列腺癌中R-spondin家族成员的功能差异及临床特征分析。

Oncotarget Pub Date : 2025-07-25 DOI: 10.18632/oncotarget.28758

Aiden Deacon, Ava Gustafson, Allison Makovec, Ella Boytim, Gabriella von Dohlen, David Moline, Elin Kairies, Sam Kellen, Khalid Ishani, Megan L Ludwig, Emily John, Alexis Anike, Hai Dang Nguyen, Scott M Dehm, Justin M Drake, Emmanuel S Antonarakis, Justin Hwang

{"title":"Dissecting the functional differences and clinical features of R-spondin family members in metastatic prostate cancer.","authors":"Aiden Deacon, Ava Gustafson, Allison Makovec, Ella Boytim, Gabriella von Dohlen, David Moline, Elin Kairies, Sam Kellen, Khalid Ishani, Megan L Ludwig, Emily John, Alexis Anike, Hai Dang Nguyen, Scott M Dehm, Justin M Drake, Emmanuel S Antonarakis, Justin Hwang","doi":"10.18632/oncotarget.28758","DOIUrl":"10.18632/oncotarget.28758","url":null,"abstract":"This study investigates the R-spondin family of genes (RSPO1/2/3/4), a group of secreted proteins that act as Wnt regulators, and their subsequent role in advanced prostate cancer (PC). When evaluating transcriptomic data from primary and metastatic PC patients, we found that alterations in RSPO2 were more prevalent than in other RSPO family members or Wnt-regulating genes APC and CTNNB1. Further, we found that RSPO2 alterations in PCs were significantly associated with worse disease-free survival. Through our in silico modeling, RSPO2 exhibited strong positive associations with genes regulating epithelial-mesenchymal transition (EMT) and double-negative prostate cancer (DNPC), but had negative correlations with androgen receptor (AR) and AR-associated genes. Furthermore, 3D modeling of RSPO2 revealed structural differences between itself and other RSPOs. In cell lines, RSPO2 overexpression caused up-regulation of EMT pathways, including EMT-regulatory transcription factors ZEB1, ZEB2, and TWIST1. Conversely, this was not observed when CTNNB1 was overexpressed in the same models. These findings highlight that, in PC, RSPO2 functions as a unique member of the R-spondin family by promoting genes and signaling pathways associated with aggressive PC, and RSPO2 amplifications are associated with poor outcomes in PC patients.","PeriodicalId":19499,"journal":{"name":"Oncotarget","volume":"16 ","pages":"606-620"},"PeriodicalIF":0.0,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12406459/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144715170","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

Comprehensive genomic profiling of over 10,000 advanced solid tumors. 1万多个晚期实体瘤的全面基因组分析。

Oncotarget Pub Date : 2025-07-25 DOI: 10.18632/oncotarget.28757

Jean-Paul De La O, Jess R Hoag, Angela K Deem, Min Wang, Arthur Starodynov, Sameer S Udhane, Janine R LoBello, Nishitha Therala, David W Hall, Gargi D Basu, Frederick L Baehner

{"title":"Comprehensive genomic profiling of over 10,000 advanced solid tumors.","authors":"Jean-Paul De La O, Jess R Hoag, Angela K Deem, Min Wang, Arthur Starodynov, Sameer S Udhane, Janine R LoBello, Nishitha Therala, David W Hall, Gargi D Basu, Frederick L Baehner","doi":"10.18632/oncotarget.28757","DOIUrl":"10.18632/oncotarget.28757","url":null,"abstract":"Purpose: To summarize clinically relevant genomic alterations in solid tumor samples from over 10,000 patients.Methods: Descriptive statistics were used to summarize findings of retrospectively analyzed OncoExTra assay data from solid tumor samples.Results: The analysis cohort included 11,091 solid tumor samples from 10,768 patients. Therapeutically actionable alterations were present in 92.0% of patient samples. Biomarkers associated with on- or off-label FDA-approved therapies were detected in 29.2% and 28.0% of samples, respectively. The prevalence of hotspot alterations detected at variant allele frequency (VAF) <5% was analyzed among 7,481 samples (67.5%) harboring ≥1 of these events: 13.7% (1,022 of 7,481) had ≥1 alteration detected at VAF <5%, and 9.8% (558 of 5,690) of hotspot alterations associated with an on- or off-label FDA-approved therapy were detected at VAF <5%. Common and rare mutations in the TERT promoter were found in 8.4% (933) of samples. Whole transcriptome sequencing detected clinically relevant fusions in 7.5% of samples, with highest frequencies in prostate cancer (42.0%). The METe14 transcript was found in 14 NSCLC samples (2.7%).Conclusions: The broad capabilities of the OncoExTra assay detected therapeutically actionable and other clinically relevant genomic events that can inform clinical decision-making for patients with advanced solid tumors.","PeriodicalId":19499,"journal":{"name":"Oncotarget","volume":"16 ","pages":"587-603"},"PeriodicalIF":0.0,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12406462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144715169","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

Retraction: Progesterone and calcitriol reduce invasive potential of endometrial cancer cells by targeting ARF6, NEDD9 and MT1-MMP. 收缩：孕酮和骨化三醇通过靶向ARF6、NEDD9和MT1-MMP降低子宫内膜癌细胞的侵袭潜力。

Oncotarget Pub Date : 2025-07-25 DOI: 10.18632/oncotarget.28760

Sana Waheed, Batsukh Dorjbal, Chad A Hamilton, G Larry Maxwell, Gustavo C Rodriguez, Viqar Syed

引用次数: 0

Extracorporeal blood filtration leading to tumor growth arrest and reduced analgesic requirements in Stage IV poorly differentiated pancreatic adenocarcinoma: A case report. 体外血液过滤导致IV期低分化胰腺腺癌肿瘤生长停止和镇痛需求减少：1例报告。

Oncotarget Pub Date : 2025-07-23 DOI: 10.18632/oncotarget.28756

Susanna Ulahannan, Peyton Smith, Jennifer Rios, Lakhmir Chawla

{"title":"Extracorporeal blood filtration leading to tumor growth arrest and reduced analgesic requirements in Stage IV poorly differentiated pancreatic adenocarcinoma: A case report.","authors":"Susanna Ulahannan, Peyton Smith, Jennifer Rios, Lakhmir Chawla","doi":"10.18632/oncotarget.28756","DOIUrl":"10.18632/oncotarget.28756","url":null,"abstract":"Background: Despite significant strides in the management of metastatic solid tumors over the past few decades, metastatic disease remains a major clinical challenge, often leading to unfavorable patient outcomes. Circulating tumor cells (CTCs), which shed from the primary tumor, have the potential to disseminate and establish distant metastases, contributing to disease progression and reduced survival rates. Removal of CTCs via extracorporeal blood filtration could have significant therapeutic implications.Case: A 51-year-old woman was diagnosed with metastatic poorly differentiated adenocarcinoma after presenting with severe abdominal pain. She deferred conventional chemotherapy options and elected treatment with CTC removal using an extracorporeal blood filter. After 9-12 filtration sessions of treatment over 12 months, she reported significant clinical improvement and staging scans demonstrated stable disease without evidence of new metastases.Conclusion: Therapeutic modalities that explore CTC removal via blood filtration may potentially have promising clinical benefits. More prospective studies are required to determine the utility of this therapeutic strategy in patients with metastatic solid tumors. Our patient demonstrated significant clinical improvement with scans demonstrating stable disease.","PeriodicalId":19499,"journal":{"name":"Oncotarget","volume":"16 ","pages":"582-586"},"PeriodicalIF":0.0,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12285521/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144691135","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

Statins exhibit anti-tumor potential by modulating Wnt/β-catenin signaling in colorectal cancer. 他汀类药物通过调节Wnt/β-catenin信号在结直肠癌中表现出抗肿瘤潜能。

Oncotarget Pub Date : 2025-07-21 DOI: 10.18632/oncotarget.28755

Sneha Tripathi, Ekta Gupta, Rutika Naik, Satyajeet Khare, Rafeeq Mir, Siddhesh Kamat, Sanjeev Galande

{"title":"Statins exhibit anti-tumor potential by modulating Wnt/β-catenin signaling in colorectal cancer.","authors":"Sneha Tripathi, Ekta Gupta, Rutika Naik, Satyajeet Khare, Rafeeq Mir, Siddhesh Kamat, Sanjeev Galande","doi":"10.18632/oncotarget.28755","DOIUrl":"10.18632/oncotarget.28755","url":null,"abstract":"Colorectal cancer remains the second leading cause of cancer-related deaths worldwide, highlighting the urgent need for more effective therapies and a deeper understanding of its molecular basis. Drug repurposing has gained traction as a viable strategy to target dysregulated oncogenic pathways. Statins, commonly prescribed for lowering cholesterol, have recently shown potential anti-cancer effects. In this study, we explore how statin treatment influences lipid metabolism, gene expression, and proteomic profiles in colorectal cancer models. Our findings provide direct evidence that statins selectively modulate key components of the Wnt/β-catenin signaling pathway, a major driver of adenoma formation, including members of the special AT-rich sequence-binding (SATB) protein family. We show that statin treatment downregulates SATB1, a known promoter of tumorigenesis in the context of Wnt activation, while simultaneously upregulating SATB2, which plays an opposing role. This reciprocal regulation shifts cellular phenotypes between epithelial and mesenchymal states in 3D spheroid models. Together, these results highlight the therapeutic potential of statins in colorectal cancer and support their consideration in drug repurposing approaches.","PeriodicalId":19499,"journal":{"name":"Oncotarget","volume":"16 ","pages":"562-581"},"PeriodicalIF":0.0,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12279029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144675402","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

microRNAs in soft tissue sarcoma: State of the art and barriers to translation. 软组织肉瘤中的microrna：最新进展和翻译障碍。

Oncotarget Pub Date : 2025-07-16 DOI: 10.18632/oncotarget.28754

Elizaveta K Titerina, Alessandro La Ferlita, Joal D Beane

引用次数: 0

A novel anti-human CD25 mAb with preferential reactivity to activated T regulatory cells depletes them from the tumor microenvironment. 一种新型抗人CD25单抗对活化的T调节性细胞具有优先反应性，可将其从肿瘤微环境中清除。

Oncotarget Pub Date : 2025-07-09 DOI: 10.18632/oncotarget.28752

Maja Buszko, Madalyn Jones, Sruthi Chempati, Lyra Morina, Kirstin Ward, Habtom Habte, Michael Dziegielewski, Ethan M Shevach

{"title":"A novel anti-human CD25 mAb with preferential reactivity to activated T regulatory cells depletes them from the tumor microenvironment.","authors":"Maja Buszko, Madalyn Jones, Sruthi Chempati, Lyra Morina, Kirstin Ward, Habtom Habte, Michael Dziegielewski, Ethan M Shevach","doi":"10.18632/oncotarget.28752","DOIUrl":"10.18632/oncotarget.28752","url":null,"abstract":"Treg play a deleterious role in the tumor microenvironment by suppressing anti-tumor effector T cells. Deletion of Treg can result in an enhanced anti-tumor response. It has been difficult to identify a cell surface antigen that is uniquely expressed on Treg which can be targeted by a deleting mAb. We immunized mice with human Treg cells which had been activated and expanded in vitro. One hybridoma (2B010) which recognized CD25 was identified. 2B010 demonstrated selective reactivity to Treg cells that had been expanded in culture for 5 days, but displayed similar reactivity to a conventional anti-CD25 mAb on freshly expanded Treg. 2B010 did not block the binding of IL-2 in the STAT5 phosphorylation assay and had no effect on the proliferation of Tconv or on Treg suppressor function. It selectively reacted with Treg activated in vivo during xeno-GVHD and produced a selective deletion of Treg from mice undergoing xeno-GVHD. Administration of 2B010 to tumor bearing humanized mice resulted in a profound depletion of Treg from the TME and activation of CD8+ T cells. No effect on tumor growth was observed. 2B010 represents a candidate for treatment of patients with cancer either alone or together with check point inhibitors.","PeriodicalId":19499,"journal":{"name":"Oncotarget","volume":"16 ","pages":"545-558"},"PeriodicalIF":0.0,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12243931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144601137","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