Cancer Communications最新文献

{"title":"DKK1 Suppresses Hippo Signaling via PIP₃-OGT-LRP6 <i>O</i>-GlcNAcylation in Hepatocellular Carcinoma.","authors":"Ukjin Lee, Jung Woo Eun, Taehee Kim, Hyewon Shim, Yunho Choi, Hyeryeon Jung, Jaewoo Mo, Soon Sun Kim, Geum Ok Baek, Moon Gyeong Yoon, Hyeyoon Lee, Wonhwa Lee, Wantae Kim, Junil Kim, Eugene C Yi, Seung Up Kim, Jae Youn Cheong, Eek-Hoon Jho","doi":"10.34133/cancomm.0022","DOIUrl":"https://doi.org/10.34133/cancomm.0022","url":null,"abstract":"","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":"46 ","pages":"0022"},"PeriodicalIF":24.9,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13112786/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147762306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Camrelizumab Plus Nab-paclitaxel in Patients with Previously Treated Advanced Urothelial Carcinoma: A Multicenter Phase II Study.","authors":"Haifeng Li, Meiting Chen, Riqing Huang, Qixiang Rong, Jing Hao, Qiufan Zheng, Yanhong Su, Ditian Shu, Yue Zhang, Wei Yang, Xuefen Lei, Yuchen Cai, Cong Xue, Xin An, Yanxia Shi","doi":"10.34133/cancomm.0025","DOIUrl":"https://doi.org/10.34133/cancomm.0025","url":null,"abstract":"<p><p><b>Background:</b> Immune checkpoint inhibitor (ICI) plus nab-paclitaxel has emerged as a promising strategy for advanced urothelial carcinoma (aUC). This study investigates the efficacy and safety of camrelizumab combined with nab-paclitaxel in patients with aUC who had progressed following first-line treatment. <b>Methods:</b> This multicenter, phase II study enrolled patients with aUC who had previously received at least 1 platinum-based therapy. Patients with prior ICI-based therapies were also included. Participants received 200 mg of camrelizumab on day 1 (D1) and 125 mg/m² of nab-paclitaxel on D1 and D8, on a 21-d cycle, until disease progression or unacceptable toxicity. The primary end point was progression-free survival (PFS). Potential biomarkers were identified through targeted gene sequencing and by quantifying pretreatment serum levels of cytokines, chemokines, growth factors, and other soluble proteins. <b>Results:</b> From 2020 June 12 to 2024 April 1, a total of 60 eligible patients were enrolled. The median age was 62.5 years, 44 patients (73.33%) were male, 44 patients (73.33%) had upper tract urothelial carcinoma, and 17 patients (28.33%) received ICI-based therapies before recruitment. After a median follow-up of 27.50 months (95% confidence interval [CI], 21.90-not reached [NR]), 47 patients (78.33%) experienced disease progression. The median PFS and overall survival were 4.66 months (95% CI, 4.13 to 8.50 months) and 15.70 months (95% CI, 12.17-NR) in the full analysis set, respectively. In addition, the median PFS and overall survival were 6.45 (95% CI, 4.30 to 9.98) months and 17.98 (95% CI, 15.44-NR) months in the per-protocol set, respectively. The objective response rate was 37.04%, with 4 patients achieving complete responses and 16 patients achieving partial responses. Notably, 15 patients experienced durable responses lasting over 1 year. Adverse events of any grade occurred in 59 patients (98.33%), while grade ≥3 adverse events were reported in 31 patients (51.67%). One patient experienced immune-related pneumonia. Biomarker analyses suggested that the elevated pretreatment serum levels of cluster of differentiation 25, interleukin-6, and insulin-like growth factor binding protein 2 were associated with worse treatment responses. <b>Conclusions:</b> Camrelizumab plus nab-paclitaxel demonstrated modest antitumor activity along with manageable toxicity in patients with previously treated aUC. <b>Trial registration:</b> This trial was registered at www.chictr.org.cn (Identifier: CTR2000033820, registration date: 2020 June 13).</p>","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":"46 ","pages":"0025"},"PeriodicalIF":24.9,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13096681/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147762310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First-Line Tislelizumab Combined with Bevacizumab and CAPOX for Metastatic Gastroesophageal Adenocarcinoma with Low Programmed Death-Ligand 1 Expression.","authors":"Ru Jia, Yan-Rong Wang, Fang-Fang Liu, Yue Ma, Hai-Yan Si, Lu Han, Miao-Miao Gou, Zhao-Li Tan, Nan Zhang, Guo-Chao Deng, Meng-Jiao Fan, Yue Shi, Yao-Yue Zhang, Yu-Shan Jia, Jun-Nan Xu, Xiao-Xing Su, Quan-Li Han, Zhi-Kuan Wang, Guang-Hai Dai","doi":"10.34133/cancomm.0024","DOIUrl":"https://doi.org/10.34133/cancomm.0024","url":null,"abstract":"","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":"46 ","pages":"0024"},"PeriodicalIF":24.9,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13084058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harnessing the Power of CAR-NK Cells for Solid Tumors: Challenges, Innovations, and Future Frontiers in Immunotherapy.","authors":"Mengchao An, Jiayao Yan, Baorui Liu, Qin Liu","doi":"10.34133/cancomm.0023","DOIUrl":"https://doi.org/10.34133/cancomm.0023","url":null,"abstract":"<p><p>Solid tumors remain a formidable challenge in cancer therapy, often evading even the most advanced immunotherapies. Natural killer (NK) cells, cytotoxic innate lymphocytes capable of recognizing and eliminating tumor cells without prior antigen sensitization, have emerged as a compelling alternative to T cells in adoptive cell therapy. Compared to chimeric antigen receptor (CAR)-T cells, CAR-engineered NK cells offer distinct advantages, including a substantially reduced risk of graft-versus-host disease (GvHD) and cytokine release syndrome (CRS). These features enable the development of \"off-the-shelf\" allogeneic cell products with improved safety and accessibility. Early clinical studies of CAR-NK cells have demonstrated encouraging efficacy in hematological malignancies alongside an excellent safety profile, fueling enthusiasm to extend this approach to solid tumors. However, the efficacy of CAR-NK cell therapy against solid tumors is limited by multiple barriers, including the immunosuppressive tumor microenvironment, poor infiltration, and persistence of NK cells in tumor tissues, heterogeneity of tumor antigen expression leading to immune escape, and the potential for NK cell dysfunction or exhaustion in chronic tumor settings. To overcome these obstacles, innovative engineering strategies are being developed. Approaches include armoring CAR-NK cells to resist tumor-induced immunosuppression, enhancing their trafficking and persistence, designing multi-antigen-targeted receptors, and incorporating built-in safety switches. This review highlights CAR-NK antitumor mechanisms, examines key challenges in solid tumor applications, and discusses cutting-edge advances and combination strategies aimed at unlocking the full therapeutic potential of CAR-NK cells. By addressing these challenges, CAR-NK cell therapy could open a new frontier in solid tumor immunotherapy.</p>","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":"46 ","pages":"0023"},"PeriodicalIF":24.9,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13067545/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147670493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proliferation and Apoptosis Adaptor Protein 15 (PEA15), a Potential Oncogenic Regulator of VHL and HIF1A Identified through Proteomic Analysis in Hepatocellular Carcinoma.","authors":"Yun Seong Jeong, Ji-Hyun Shin, Soo Mi Kim, Bo Hwa Sohn, Sun Young Yim, Ji Hoon Kim, Jae Jun Shim, Sung Hwan Lee, Yun Shin Chun, Sunyoung S Lee, Hui Dai, Ahmed Kaseb, Koo Jeong Kang, Holger K Eltzschig, A Robert MacLeod, Xiaolin Luo, Alexey Revenko, Youngsoo Kim, Ju-Seog Lee","doi":"10.34133/cancomm.0020","DOIUrl":"10.34133/cancomm.0020","url":null,"abstract":"<p><p><b>Background:</b> Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths globally. Although the hypoxia-inducible factor 1A (HIF1A) pathway is crucial in HCC progression, its regulatory mechanisms remain unclear as mutations in its primary regulator, von Hippel-Lindau tumor suppressor (<i>VHL</i>), are rare in HCC. We aimed to elucidate the role of proliferation and apoptosis adaptor protein 15 (PEA15), identified through proteomic analysis, as a regulator of the VHL/HIF1A pathway and a therapeutic target in HCC. <b>Methods:</b> Proteomic and genomic analyses of over 1,000 HCC samples were conducted, identifying <i>PEA15</i> amplification. Functional validation involved in vitro and in vivo assays, including gene knockdown, ectopic expression, and antisense oligonucleotide (ASO) therapy in xenograft models. Protein interactions were assessed using immunoprecipitation and ubiquitination assays. <b>Results:</b> We identified 3 clinically distinct HCC subtypes and found that <i>PEA15</i> was selectively amplified and highly expressed in the mesenchymal (MES) subtype, which exhibited the poorest prognosis. <i>PEA15</i> acted as a regulator of the VHL/HIF1A pathway and a key oncogene in HCC. The amplification of <i>PEA15</i> was significantly associated with the poor survival of HCC patients. Moreover, by interacting with the β-domain of VHL, PEA15 promoted HCC cell proliferation and migration by inhibiting VHL's interaction with the VHL/elongin C (ELOC)/elongin B (ELOB)/cullin 2 (CUL2) E3 ligase complex, destabilizing the complex and consequently activating HIF1A. Importantly, pharmacologically inhibiting PEA15 using <i>PEA15</i> ASO drugs attenuated tumor burden and restored VHL function in a xenograft mouse model. <b>Conclusions:</b> This study identified <i>PEA15</i> as a potential oncogene in HCC, regulating the VHL/HIF1A axis and driving tumor progression. Targeting <i>PEA15</i> using ASOs offers a promising therapeutic strategy for HCC, particularly in the MES subtype. These findings provide a basis for further exploration of <i>PEA15</i>-targeted therapies to improve HCC outcomes.</p>","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":"46 ","pages":"0020"},"PeriodicalIF":24.9,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13058230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147643571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Roles of Protein <i>S</i>-Palmitoylation in Cancers: From Dynamic Modulation to Therapeutic Potential.","authors":"Haonan Zheng, Xiaoyu Sun, Yang Gao, Qinbiao Wang, Jiaqi Wang, Minjie Wei, Yu Tang, Miao He","doi":"10.34133/cancomm.0017","DOIUrl":"https://doi.org/10.34133/cancomm.0017","url":null,"abstract":"<p><p>Protein <i>S</i>-palmitoylation is a highly conserved posttranslational lipid modification that occurs on cysteine residues and critically influences protein maturation, subcellular localization, trafficking, and stability. Owing to its unique reversibility and dynamic nature, <i>S</i>-palmitoylation plays a pivotal role in cancer. This review comprehensively summarized the expression profiles and distribution of key cancer-related <i>S</i>-palmitoylation enzymes in recent years. Importantly, we highlight the specific mechanisms by which the dual states of palmitoylation and depalmitoylation function as a dynamic regulatory axis during the transformation of cancer cells into cancer stem cells and during the transition from a normal tissue environment to a tumor microenvironment. Furthermore, we discussed emerging therapeutic strategies targeting <i>S</i>-palmitoylation, including the development of specific inhibitors and competitive blockade of substrate-binding sites, which offer additional insights into the translational potential of <i>S</i>-palmitoylation as a therapeutic target for cancer.</p>","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":"46 ","pages":"0017"},"PeriodicalIF":24.9,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13044351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147621754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rezivertinib in <i>EGFR</i>-Mutated Non-Small Cell Lung Cancer Patients with Central Nervous System Metastasis: Central Nervous System Efficacy from the Phase III REZOR Study.","authors":"Sheng Yang, Yanqiu Zhao, Meili Sun, Minghong Bi, Bo Zhu, Zhaohong Chen, Huiqing Yu, Liangming Zhang, Lin Wu, Rui Zhou, Wenxiu Yao, Xingya Li, Zhigang Han, Ke Wang, Lijun Wang, Meiling Wen, Yanzhen Guo, Yingcheng Lin, Shenghua Sun, Shuliang Guo, Tienan Yi, Wenhua Zhao, Zhuang Yu, Jianwen Qin, Yueyin Pan, Zhiyong He, Feng Ye, Huaqiu Shi, Jian Fang, Rui Ma, Hong Lu, Hua Zhang, Jianhua Shi, Jinghua Gao, Jiuwei Cui, Manxiang Li, Shanyong Yi, Shundong Cang, Yongqian Shu, Don Zhang, Jirong Peng, Feng Gao, Tingting Wang, Anqi Zhou, Yuankai Shi","doi":"10.34133/cancomm.0018","DOIUrl":"https://doi.org/10.34133/cancomm.0018","url":null,"abstract":"<p><p><b>Background:</b> From 2019 July 15 to 2022 February 14, the REZOR study enrolled 369 treatment-naïve patients with locally advanced or metastatic non-small cell lung cancer harboring <i>EGFR</i> mutations (exon 19 deletion or L858R mutation). Patients were randomly assigned 1:1 to receive either rezivertinib (180 mg/d) plus gefitinib placebo or gefitinib (250 mg/d) plus rezivertinib placebo. Previous results demonstrated significantly improved progression-free survival (PFS) with rezivertinib versus gefitinib and a favorable safety profile. Here, we update the analyses of central nervous system (CNS) outcomes in patients with baseline CNS metastases. <b>Methods:</b> All patients underwent brain magnetic resonance imaging at baseline and each subsequent efficacy evaluation until radiological disease progression or any other treatment discontinuation criteria were met. <i>EGFR</i> mutation status was determined by testing using tissue or plasma samples during screening. Patients with stable, asymptomatic CNS metastasis were eligible for enrollment. The CNS full analysis set (cFAS) comprised patients with baseline CNS metastasis identified on magnetic resonance imaging and evaluated by blinded independent central review according to the Response Assessment in Neuro-Oncology Brain Metastases criteria. Patients with measurable CNS target lesions formed the CNS evaluable-for-response set (cEFR). <b>Results:</b> As of the 2023 November 30 data cutoff, 159 patients had baseline CNS metastasis in the cFAS (rezivertinib: <i>n</i> = 81; gefitinib: <i>n</i> = 78) and 25 in the cEFR (rezivertinib: <i>n</i> = 12; gefitinib: <i>n</i> = 13) per blinded independent central review. In the cFAS, 59 CNS PFS events occurred (rezivertinib: <i>n</i> = 30; gefitinib: <i>n</i> = 29). Median CNS PFS was significantly longer with rezivertinib (24.9 months; 95% confidence interval [CI], 16.5 months-not estimable [NE]) than with gefitinib (15.2 months; 95% CI, 10.5 months-NE), with a hazard ratio of 0.58 (95% CI, 0.34 to 0.99; <i>P</i> = 0.047). In the cEFR, the CNS objective response rate was 83.3% (95% CI, 51.6% to 97.9%) with rezivertinib and 76.9% (95% CI, 46.2% to 95.0%) with gefitinib (odds ratio = 1.50; 95% CI, 0.20 to 11.0; <i>P</i> = 0.690). No new safety findings were observed. <b>Conclusions:</b> Rezivertinib demonstrated a statistically significant superior CNS efficacy over gefitinib as first-line treatment in advanced <i>EGFR</i>-mutated non-small cell lung cancer patients with baseline CNS metastases. The safety profile was consistent with previous analyses. <b>Trial registration:</b> NCT03866499 (ClinicalTrials.gov).</p>","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":"46 ","pages":"0018"},"PeriodicalIF":24.9,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13036320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147590194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TOPK Suppresses the CD8⁺ T Cell Antitumor Immunity via Modulation of IRF5 Expression.","authors":"Nianke Zang, Jinfeng Gan, Ye Chen, Zheng Huang, Chichu Xie, Junlong Dang, Changyuan Huang, Linjie Yang, Xuelian Chen, Guangli Rong, Jianbo Sun, Yiming Shao, Julie Wang, Guangying Qi, Yu Liu, Song Guo Zheng","doi":"10.34133/cancomm.0021","DOIUrl":"https://doi.org/10.34133/cancomm.0021","url":null,"abstract":"<p><p><b>Background:</b> T-LAK cell-originated protein kinase (TOPK), a serine/threonine kinase, is aberrantly overexpressed in human tumors and promotes malignant proliferation. Melanoma is a highly immunogenic tumor in which CD8⁺ T cell-mediated cytotoxicity is usually less effective in tumor control and responsive to immune checkpoint blockade. It is unclear whether the expression and functional characterization of TOPK within the immune cells affect the tumor microenvironment (TME) in patients with melanoma. This study aims to elucidate the expression pattern and immunoregulatory function of TOPK in CD8⁺ T lymphocytes during antitumor responses. <b>Methods:</b> Public single-cell RNA-sequencing (scRNA-seq) dataset analysis and flow cytometry assessed TOPK in tumor-infiltrating CD8⁺ T cells from patients with melanoma. Genetic deletion and pharmacological inhibition of TOPK using HI-TOPK-032 tested T cell-mediated melanoma control. Flow cytometry and tumor cell coculture killing assays measured effector release and target-cell apoptosis. Mechanistic analyses included assessment of interferon regulatory factor 5 (IRF5) expression, together with combination therapy using a programmed cell death protein 1 (PD-1)-blocking antibody in vivo. scRNA-seq of tumor-infiltrating lymphocytes (TILs) from <i>Topk</i> ^fl/fl and <i>Cd8</i> ^Cre <i>Topk</i> ^fl/fl mice was also performed to define TOPK-dependent immune programs within the melanoma TME. <b>Results:</b> Single-cell transcriptomes identified a TOPK⁺ subset of tumor-infiltrating CD8⁺ T cells in melanoma, which was higher than that in normal lymph nodes (LNs), and exhibited suppressed cytotoxic and cytokine programs. CD8⁺ T cell-specific <i>Topk</i> deletion increased granzyme B (GzmB), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) secretion and improved tumor control. TOPK-deficient CD8⁺ T cells showed elevated activation-associated signaling pathways and immune effector gene expression. In murine TIL scRNA-seq, <i>Cd8</i> ^Cre <i>Topk</i> ^fl/fl tumors exhibited increased effector and activation programs, reduced exhaustion and dysfunction programs, and enhanced immune crosstalk in the TME. Mechanistically, TOPK suppressed IRF5 expression and HI-TOPK-032 restored CD8⁺ T cell cytotoxicity in vitro and, with anti-PD-1, further inhibited tumor growth and increased intratumoral cytokine production. In human CD8⁺ T cells, enforced TOPK expression impaired cytotoxicity and cytokine secretion, reversed by IRF5 coexpression. <b>Conclusions:</b> These findings establish TOPK as the immune checkpoint limiting CD8⁺ T cell functionality in tumors and indicate the potential of TOPK inhibition as a strategy to augment T cell-based immunotherapies.</p>","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":"46 ","pages":"0021"},"PeriodicalIF":24.9,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13003159/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147497595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revolutionary ctDNA-Guided Therapy Adaptation in <i>ESR1</i>-Mutated Advanced Breast Cancer: Insights from the Initial SERENA-6 Trial.","authors":"Lulu Yang, Ning Zhu, Ying Yuan, Jing Zhao","doi":"10.34133/cancomm.0012","DOIUrl":"https://doi.org/10.34133/cancomm.0012","url":null,"abstract":"","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":"46 ","pages":"0012"},"PeriodicalIF":24.9,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12982825/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147466786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IMMUNOSARC II Master Trial: Phase II Study of Sunitinib and Nivolumab in Clear Cell Sarcoma Cohort.","authors":"Javier Martin-Broto, Sandra J Strauss, Emanuela Palmerini, Claudia Valverde, Ana Sebio, Andres Redondo, Silvia Stacchiotti, Giovanni Grignani, Sandra Aliberti, Roberto Diaz-Beveridge, Enrique Gonzalez Billalabeitia, Josefina Cruz, Irene Carrasco-Garcia, Toni Ibrahim, Juan Diaz-Martin, Carmen Salguero-Aranda, Antonio Gutierrez, Empar Mayordomo-Aranda, Rafael Ramos, Jose Merino, Paola Collini, Roberto Tirabosco, Silvia Bague, Cleofe Romagosa, Maria Augusta Carrera, Patricio Ledesma, Nadia Hindi, David Silva Moura","doi":"10.34133/cancomm.0015","DOIUrl":"https://doi.org/10.34133/cancomm.0015","url":null,"abstract":"<p><p><b>Background:</b> Clear cell sarcoma (CCS) is an ultrarare sarcoma driven by a specific chromosomal translocation, most commonly the EWS RNA binding protein 1-activating transcription factor 1 fusion (<i>EWSR1::ATF1</i>), for which chemotherapy shows limited activity, with a median progression-free survival (PFS) of approximately 3 months in retrospective series. In the present trial, a CCS cohort was selected based on signals of activity observed in the IMMUNOSARC I phase I/II trial evaluating nivolumab in combination with sunitinib in sarcomas. <b>Methods:</b> Patients aged 12 to 80 years with advanced, progressive, and measurable CCSs were enrolled after central pathology review, and molecular confirmation of an <i>EWSR1</i> rearrangement was required. Sunitinib was administered at 37.5 mg/d during the first 2 weeks and then at 25 mg/d along with nivolumab at 240 mg every 2 weeks. The primary end point was the 6-month PFS rate, defined under the null (H₀) and alternative (H₁) hypotheses as 25% and 55%, respectively. Under Simon's 2-stage minimax design (α = 0.05, power = 0.90), a minimum of 10 of 23 patients needed to be progression-free at 6 months. <b>Results:</b> At the time of cutoff, 23 patients were evaluable for the primary end point. With a median follow-up of 23.0 months (95% confidence interval [CI], 10.0 to 35.0 months), the 6-month PFS rate was 50.1% (95% CI, 29.1% to 71.1%), while the median PFS was 6.2 months (95% CI, 3.0 to 9.3 months). Of 21 patients who underwent at least 1 radiological assessment, 3 (14.3%) achieved partial response, 14 (66.7%) had stable disease, and 4 (19.0%) had progressive disease. The median overall survival was 17.0 months (95% CI, 95% CI, 5.6 to 28.5 months). The main all-grade drug-related toxicities were lymphocytopenia (46.2%), leukopenia (38.5%), anemia (38.5%), and neutropenia (38.5%). Two grade 4 toxicities were reported: Alanine aminotransferase increased and ischemia (each 3.8%), while 31 grade 3 toxicities occurred, with anemia and lymphocytopenia being the most common (each 23.1%). A higher programmed death-ligand 1 composite score was associated with better PFS: 21.2 months (95% CI, 6.0 to 36.4 months) versus 4.2 months (95% CI, 2.7 to 5.6 months), <i>P</i> = 0.045. <b>Conclusions:</b> While further studies are needed, initial findings suggest that nivolumab plus sunitinib could be a valuable addition to the current armamentarium for CCS management. <b>Trial registration:</b> ClinicalTrials.gov ID NCT03277924 (date of registration: 2017 September 6).</p>","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":"46 ","pages":"0015"},"PeriodicalIF":24.9,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12981246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147466837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}