Oncotarget最新文献_第7页

Targeting the multifaceted BRAF in cancer: New directions. 靶向癌症中多方面的 BRAF：新方向。

Oncotarget Pub Date : 2024-07-16 DOI: 10.18632/oncotarget.28612

Eamon Toye, Alexander Chehrazi-Raffle, Justin Hwang, Emmanuel S Antonarakis

引用次数: 0

How to deal with runaway metastatic disease? 如何应对失控的转移性疾病？

Oncotarget Pub Date : 2024-07-12 DOI: 10.18632/oncotarget.28609

Justine Paris, Guilhem Bousquet

引用次数: 0

INT-1B3, an LNP formulated miR-193a-3p mimic, promotes anti-tumor immunity by enhancing T cell mediated immune responses via modulation of the tumor microenvironment and induction of immunogenic cell death. INT-1B3是一种LNP配制的miR-193a-3p模拟物，它通过调节肿瘤微环境和诱导免疫原性细胞死亡，增强T细胞介导的免疫反应，从而促进抗肿瘤免疫。

Oncotarget Pub Date : 2024-07-12 DOI: 10.18632/oncotarget.28608

Chantal L Duurland, Thijs de Gunst, Harm C den Boer, Marion T J van den Bosch, Bryony J Telford, Rogier M Vos, Xiaolei Xie, Mingfa Zang, Fang Wang, Yingying Shao, Xiaoyu An, Jingjing Wang, Jie Cai, Ludovic Bourré, Laurens A H van Pinxteren, Roel Q J Schaapveld, Michel Janicot, Sanaz Yahyanejad

{"title":"INT-1B3, an LNP formulated miR-193a-3p mimic, promotes anti-tumor immunity by enhancing T cell mediated immune responses via modulation of the tumor microenvironment and induction of immunogenic cell death.","authors":"Chantal L Duurland, Thijs de Gunst, Harm C den Boer, Marion T J van den Bosch, Bryony J Telford, Rogier M Vos, Xiaolei Xie, Mingfa Zang, Fang Wang, Yingying Shao, Xiaoyu An, Jingjing Wang, Jie Cai, Ludovic Bourré, Laurens A H van Pinxteren, Roel Q J Schaapveld, Michel Janicot, Sanaz Yahyanejad","doi":"10.18632/oncotarget.28608","DOIUrl":"10.18632/oncotarget.28608","url":null,"abstract":"microRNAs (miRNAs) are small, non-coding RNAs that regulate expression of multiple genes. MiR-193a-3p functions as a tumor suppressor in many cancer types, but its effect on inducing specific anti-tumor immune responses is unclear. Therefore, we examined the effect of our lipid nanoparticle (LNP) formulated, chemically modified, synthetic miR-193a-3p mimic (INT-1B3) on anti-tumor immunity. INT-1B3 inhibited distant tumor metastasis and significantly prolonged survival. INT-1B3-treated animals were fully protected against challenge with autologous tumor cells even in absence of treatment indicating long-term immunization. Protection against autologous tumor cell challenge was hampered upon T cell depletion and adoptive T cell transfer abrogated tumor growth. Transfection of tumor cells with our miR-193a-3p mimic (1B3) resulted in tumor cell death and apoptosis accompanied by increased expression of DAMPs. Co-culture of 1B3-transfected tumor cells and immature DC led to DC maturation and these mature DC were able to stimulate production of type 1 cytokines by CD4+ and CD8+ T cells. CD4-CD8- T cells also produced type 1 cytokines, even in response to 1B3-transfected tumor cells directly. Live cell imaging demonstrated PBMC-mediated cytotoxicity against 1B3-transfected tumor cells. These data demonstrate for the first time that miR-193a-3p induces long-term immunity against tumor development via modulation of the tumor microenvironment and induction of immunogenic cell death.","PeriodicalId":19499,"journal":{"name":"Oncotarget","volume":"15 ","pages":"470-485"},"PeriodicalIF":0.0,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11247534/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141616906","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

Correction: Cyclin E/Cdk2-dependent phosphorylation of Mcl-1 determines its stability and cellular sensitivity to BH3 mimetics. 更正：依赖于 Cyclin E/Cdk2 的 Mcl-1 磷酸化决定了其稳定性和细胞对 BH3 模拟物的敏感性。

Oncotarget Pub Date : 2024-07-12 DOI: 10.18632/oncotarget.28593

Gaurav S Choudhary, Trinh T Tat, Saurav Misra, Brian T Hill, Mitchell R Smith, Alexandru Almasan, Suparna Mazumder

引用次数: 0

The advances in targeting CD47/SIRPα "do not eat me" axis and their ongoing challenges as an anticancer therapy. 针对 CD47/SIRPα "别吃我 "轴的研究进展及其作为抗癌疗法所面临的挑战。

Oncotarget Pub Date : 2024-07-10 DOI: 10.18632/oncotarget.28607

Maria Gracia-Hernandez, Manasa Suresh, Alejandro Villagra

引用次数: 0

Improved efficacy of pembrolizumab combined with soluble EphB4-albumin in HPV-negative EphrinB2 positive head neck squamous cell carcinoma. pembrolizumab联合可溶性EphB4-白蛋白对HPV阴性EphrinB2阳性头颈部鳞状细胞癌的疗效提高。

Oncotarget Pub Date : 2024-07-10 DOI: 10.18632/oncotarget.28605

Alexandra Jackovich, Barbara J Gitlitz, Justin Wayne Wong Tiu-Lim, Vinay Duddalwar, Kevin George King, Anthony B El-Khoueiry, Jacob Stephen Thomas, Denice Tsao-Wei, David I Quinn, Parkash S Gill, Jorge J Nieva

{"title":"Improved efficacy of pembrolizumab combined with soluble EphB4-albumin in HPV-negative EphrinB2 positive head neck squamous cell carcinoma.","authors":"Alexandra Jackovich, Barbara J Gitlitz, Justin Wayne Wong Tiu-Lim, Vinay Duddalwar, Kevin George King, Anthony B El-Khoueiry, Jacob Stephen Thomas, Denice Tsao-Wei, David I Quinn, Parkash S Gill, Jorge J Nieva","doi":"10.18632/oncotarget.28605","DOIUrl":"10.18632/oncotarget.28605","url":null,"abstract":"Objective: Patients with relapsed or metastatic head and neck squamous cell carcinoma (HNSCC) after primary local therapy have low response rates with cetuximab, systemic chemotherapy or check point inhibitor therapy. Novel combination therapies with the potential to improve outcomes for patients with HNSCC is an area of high unmet need.Methods: This is a phase II single-arm clinical trial of locally advanced or metastatic HNSCC patients treated with a combination of soluble EphB4-human serum albumin (sEphB4-HSA) fusion protein and pembrolizumab after platinum-based chemotherapy with up to 2 prior lines of treatment. The primary endpoints were safety and tolerability and the primary efficacy endpoint was overall response rate (ORR). Secondary endpoints included progression free survival (PFS) and overall survival (OS). HPV status and EphrinB2 expression were evaluated for outcome.Results: Twenty-five patients were enrolled. Median follow up was 40.4 months (range 9.8 - 40.4). There were 6 responders (ORR 24%). There were 5 responders in the 11 HPV-negative and EphrinB2 positive patients, (ORR 45%) with 2 of these patients achieving a complete response (CR). The median PFS in HPV-negative/EphrinB2 positive patients was 3.2 months (95% CI 1.1, 7.3). Median OS in HPV-negative/EphrinB2 positive patients was 10.9 months (95% CI 2.0, 13.7). Hypertension, transaminitis and fatigue were the most common toxicities.Discussion: The combination of sEphB4-HSA and pembrolizumab has a favorable toxicity profile and favorable activity particularly among HPV-negative EphrinB2 positive patients with HNSCC.","PeriodicalId":19499,"journal":{"name":"Oncotarget","volume":"15 ","pages":"444-458"},"PeriodicalIF":0.0,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11235133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141563993","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: Superior efficacy of the antifungal agent ciclopirox olamine over gemcitabine in pancreatic cancer models. 撤回：在胰腺癌模型中，抗真菌剂环吡酮胺的疗效优于吉西他滨。

Oncotarget Pub Date : 2024-07-10 DOI: 10.18632/oncotarget.28601

Chrysovalantou Mihailidou, Pavlos Papakotoulas, Athanasios G Papavassiliou, Michalis V Karamouzis

引用次数: 0

Genotype matters: Personalized screening recommendations for germline CHEK2 variants. 基因型很重要：CHEK2基因变异的个性化筛查建议。

Oncotarget Pub Date : 2024-07-10 DOI: 10.18632/oncotarget.28604

Adela Rodriguez Hernandez, Rochelle Scheib, Judy E Garber, Huma Q Rana, Brittany L Bychkovsky

引用次数: 0

Regorafenib synergizes with TAS102 against multiple gastrointestinal cancers and overcomes cancer stemness, trifluridine-induced angiogenesis, ERK1/2 and STAT3 signaling regardless of KRAS or BRAF mutational status. 瑞戈非尼与 TAS102 对多种胃肠道癌症具有协同作用，并且无论 KRAS 或 BRAF 突变状态如何，都能克服癌症干性、三氟利定诱导的血管生成、ERK1/2 和 STAT3 信号转导。

Oncotarget Pub Date : 2024-07-02 DOI: 10.18632/oncotarget.28602

Jun Zhang, Lanlan Zhou, Shuai Zhao, Wafik S El-Deiry

{"title":"Regorafenib synergizes with TAS102 against multiple gastrointestinal cancers and overcomes cancer stemness, trifluridine-induced angiogenesis, ERK1/2 and STAT3 signaling regardless of KRAS or BRAF mutational status.","authors":"Jun Zhang, Lanlan Zhou, Shuai Zhao, Wafik S El-Deiry","doi":"10.18632/oncotarget.28602","DOIUrl":"10.18632/oncotarget.28602","url":null,"abstract":"Single-agent TAS102 (trifluridine/tipiracil) and regorafenib are FDA-approved treatments for metastatic colorectal cancer (mCRC). We previously reported that regorafenib combined with a fluoropyrimidine can delay disease progression in clinical case reports of multidrug-resistant mCRC patients. We hypothesized that the combination of TAS102 and regorafenib may be active in CRC and other gastrointestinal (GI) cancers and may in the future provide a treatment option for patients with advanced GI cancer. We investigated the therapeutic effect of TAS102 in combination with regorafenib in preclinical studies employing cell culture, colonosphere assays that enrich for cancer stem cells, and in vivo. TAS102 in combination with regorafenib has synergistic activity against multiple GI cancers in vitro including colorectal and gastric cancer, but not liver cancer cells. TAS102 inhibits colonosphere formation and this effect is potentiated by regorafenib. In vivo anti-tumor effects of TAS102 plus regorafenib appear to be due to anti-proliferative effects, necrosis and angiogenesis inhibition. Growth inhibition by TAS102 plus regorafenib occurs in xenografted tumors regardless of p53, KRAS or BRAF mutations, although more potent tumor suppression was observed with wild-type p53. Regorafenib significantly inhibits TAS102-induced angiogenesis and microvessel density in xenografted tumors, as well inhibits TAS102-induced ERK1/2 activation regardless of RAS or BRAF status in vivo. TAS102 plus regorafenib is a synergistic drug combination in preclinical models of GI cancer, with regorafenib suppressing TAS102-induced increase in microvessel density and p-ERK as contributing mechanisms. The TAS102 plus regorafenib drug combination may be further tested in gastric and other GI cancers.","PeriodicalId":19499,"journal":{"name":"Oncotarget","volume":"15 ","pages":"424-438"},"PeriodicalIF":0.0,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11218792/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141492899","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

Using early on-treatment circulating tumor DNA measurements as response assessment in metastatic castration resistant prostate cancer. 使用早期治疗循环肿瘤 DNA 测量结果评估转移性去势抵抗性前列腺癌的反应。

Oncotarget Pub Date : 2024-07-02 DOI: 10.18632/oncotarget.28599

S H Tolmeijer, E Boerrigter, N P Van Erp, Niven Mehra

引用次数: 0