Cancer Communications最新文献

{"title":"A phase II basket trial of dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART) SWOG S1609: durable responses and delayed pseudoprogression in small cell carcinoma of the ovary, hypercalcemic type cohort.","authors":"Young Kwang Chae, Megan Othus, Sandip Pravin Patel, Raid Aljumaily, Khine Z Win, Tanya Pejovic, Sajeve S Thomas, William R Robinson, Hye Sung Kim, Liam Il-Young Chung, Christine M McLeod, Helen X Chen, Elad Sharon, Howard Streicher, Christopher W Ryan, Charles D Blanke, Razelle Kurzrock","doi":"10.1002/cac2.70020","DOIUrl":"https://doi.org/10.1002/cac2.70020","url":null,"abstract":"<p><strong>Background: </strong>The combined use of anti-programmed cell death protein 1 (PD-1)/anti-cytotoxic T-lymphocyte associated protein 4 (CTLA-4) checkpoint inhibitors has been effective in various cancer types. The Southwest Oncology Group (SWOG) Dual Anti-CTLA-4 and Anti-PD-1 Blockade in Rare Tumors (DART) S1609 study investigated ipilimumab and nivolumab in ultra-rare cancers, including small cell carcinoma of the ovary, hypercalcemic type (SCCOHT). The purpose of the study was to evaluate the potential clinical benefit of ipilimumab and nivolumab in patients with SCCOHT.</p><p><strong>Methods: </strong>DART was a prospective, open-labeled, multicenter (>1,000 US sites), multi-cohort phase II clinical trial of intravenous administration of ipilimumab (1 mg/kg, every 6 weeks) plus nivolumab (240 mg, every 2 weeks). The primary endpoint was overall response rate [ORR, confirmed complete response (CR) and partial response (PR)] per RECIST. Secondary endpoints included progression-free survival (PFS), overall survival (OS), clinical benefit rate (CBR; overall response plus stable disease ≥6 months), and toxicity. Immune responses were also evaluated.</p><p><strong>Results: </strong>Six patients (median age, 30.5 years; median, 2 prior therapies; no prior immunotherapy exposure) with advanced/metastatic SCCOHT were evaluable. ORR and CBR were both 16.7% (1/6) with one patient having a confirmed CR lasting 46.2+ months. However, another patient had a confirmed immune CR (iCR) with immune PFS (iPFS) of 53+ months [ORR/iORR, 33.3% (2/6)]. Notably, the latter patient had a progressing lesion at 24 weeks after initial response, but with renewed regression with ongoing therapy, suggesting delayed pseudo-progression. At 12-months, 3 patients remained alive. Median PFS was 1.4 months (range, 0.9 months-not reached); median OS was 14.2 months (2 months-not reached). No adverse events caused treatment discontinuation.</p><p><strong>Conclusion: </strong>Two of 6 patients (33.3%) with SCCOHT achieved durable CR/iCR and long-term survival with ipilimumab plus nivolumab. Correlative studies to determine response and resistance markers are ongoing.</p><p><strong>Clinicaltrials: </strong></p><p><strong>Gov registry: </strong>NCT02834013.</p>","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":" ","pages":""},"PeriodicalIF":20.1,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeted reactivation of the novel tumor suppressor DAPK1, an upstream regulator of p53, in high-grade serous ovarian cancer by mRNA liposomes reduces viability and enhances drug sensitivity in preclinical models.","authors":"Monika Raab, Balázs Győrffy, Samuel Peña-Llopis, Daniela Fietz, Monika Kressin, Margareta Kolaric, Matthias Ebert, Khayal Gasimli, Sven Becker, Mourad Sanhaji, Klaus Strebhardt","doi":"10.1002/cac2.70029","DOIUrl":"https://doi.org/10.1002/cac2.70029","url":null,"abstract":"","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":" ","pages":""},"PeriodicalIF":20.1,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of exposure-response-safety relationship of model-informed low-dose 500 mg abiraterone acetate in prostate cancer patients.","authors":"Edmund Chiong, Ziteng Wang, Eleanor Jing Yi Cheong, Yi Chen Yao, Sin Mun Tham, Revathi Periaswami, Poh Choo Toh, Ziting Wang, Qing Hui Wu, Woon Chau Tsang, Arshvin Kesavan, Alvin Seng Cheong Wong, Patrick Thomas Wong, Felicia Lim, Shuaibing Liu, Eric Chun Yong Chan","doi":"10.1002/cac2.70035","DOIUrl":"https://doi.org/10.1002/cac2.70035","url":null,"abstract":"","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":" ","pages":""},"PeriodicalIF":20.1,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"N⁶-methyladenosine-regulated exosome biogenesis orchestrates an immunosuppressive pre-metastatic niche in gastric cancer peritoneal metastasis.","authors":"Song Li, Jianyuan Zhou, Shuang Wang, Qian Yang, Shulun Nie, Chunwang Ji, Xue Zhang, Shuhan Li, Xuanyu Zhou, Jiahui Chu, Xuehui Wu, Jianqiao Jiao, Ruitao Xu, Qian Xu, Miao Huang, Qiushi Wang, Liliang Dou, Qinqin Hu, Fan Jiang, Xin Dai, Zhaodi Nan, Xinyu Song, Di Zhang, Lian Liu","doi":"10.1002/cac2.70034","DOIUrl":"https://doi.org/10.1002/cac2.70034","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer peritoneal metastasis is clinically challenging, given the limited treatment options and poor prognosis. The molecular mechanisms that precede gastric cancer peritoneal metastasis, known as the pre-metastatic niche (PMN), and its relationship with N⁶-methyladenosine (m⁶A) modification remain unclear.</p><p><strong>Methods: </strong>We used 87 resected gastric cancer tissues and 4 public datasets to explore the association between methyltransferase-like 3 (METTL3) expression and gastric cancer peritoneal metastasis. Roles of m⁶A, exosomes, or macrophages in PMN formation were explored in immunocompetent mouse models through exosome treatments or macrophage modifications. Key genes and regulatory mechanisms were uncovered using mass spectrometry, RNA/miRNA sequencing, RNA-immunoprecipitation, dual-luciferase assays, and point mutations in the ras-related protein Rab-27A (RAB27A) in cells. Macrophage and T-cell functions were assessed using enzyme-linked immunosorbent assay, flow cytometry, and cytotoxicity assays.</p><p><strong>Results: </strong>METTL3 overexpression in gastric cancer cells enhanced RAB27A translation by methylating its mRNA A502 base, facilitated by its m⁶A \"reader\" YTH N⁶-methyladenosine RNA binding protein F1 (YTHDF1), and led to increased exosome biogenesis. The miRNA-17-92 cluster was enriched in METTL3-overexpressed cell-derived exosomes and targeted SRC kinase signaling inhibitor 1 (SRCIN1) to activate SRC proto-oncogene, non-receptor tyrosine kinase (SRC) signaling in peritoneal macrophages. Macrophage activation skewed cytokine production towards an immunosuppressive profile in the peritoneum, elevating the levels of interleukin (IL)-10 and tumor necrosis factor (TNF) and reducing the levels of IL-1 and IL-6. These cytokine shifts inhibited T cell proliferation and cytotoxic activities, which created an immunosuppressive PMN and led to peritoneal metastasis. The association between METTL3, macrophages, and peritoneal metastasis was verified in clinical samples.</p><p><strong>Conclusions: </strong>Our study identified an intricate m⁶A-regulated mechanism of peritoneal PMN development that is mediated by exosome-promoted macrophages. These insights into gastric cancer peritoneal metastasis offer promising directions for translational research.</p>","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":" ","pages":""},"PeriodicalIF":20.1,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extranodal diffuse large B-cell lymphoma: Clinical and molecular insights with survival outcomes from the multicenter EXPECT study.","authors":"Si-Yuan Chen, Peng-Peng Xu, Ru Feng, Guo-Hui Cui, Li Wang, Shu Cheng, Rong-Ji Mu, Hui-Lai Zhang, Xiao-Lei Wei, Yong-Ping Song, Kai-Yang Ding, Li-Hua Dong, Zun-Min Zhu, Shen-Miao Yang, Xin Wang, Ting-Bo Liu, Jian-Da Hu, Xiao-Yun Zheng, Ou Bai, Jing-Yan Xu, Liang Huang, Wei Sang, Ke-Qian Shi, Fan Zhou, Fei Li, Ai-Bin Liang, Hui Zhou, Si-Guo Hao, Hong-Hui Huang, Bin Xu, Wen-Bin Qian, Cai-Xia Li, Zhi-Ming Li, Chong-Yang Wu, Xiao-Bo Wang, Wen-Yu Shi, Shu-Ye Wang, Yu-Yang Tian, Xi Zhang, Ke-Shu Zhou, Li-Juan Cui, Hui Liu, Huo Tan, Qing Leng, Dong-Lu Zhao, Ting Niu, Wei-Li Zhao","doi":"10.1002/cac2.70033","DOIUrl":"https://doi.org/10.1002/cac2.70033","url":null,"abstract":"<p><strong>Background: </strong>Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of aggressive non-Hodgkin's lymphoma with distinct clinical and molecular heterogeneity. DLBCL that arises in extranodal organs is particularly linked to poor prognosis. This study aimed to determine the clinical and molecular characteristics of extranodal involvement (ENI) in DLBCL and assess the actual survival status of the patients.</p><p><strong>Methods: </strong>In this population-based cohort study, we investigated the clinical features of 5,023 patients newly diagnosed with DLBCL. Their clinical conditions, eligibility criteria, and sociodemographic details were recorded and analyzed. Gene panel sequencing was performed on 1,050 patients to discern molecular patterns according to ENI.</p><p><strong>Results: </strong>The 2-year overall survival (OS) rate was 76.2% [95% confidence interval (CI), 74.0%-78.2%], and the 5-year OS rate was 67.9% (95% CI, 65.2%-70.4%). The primary treatment was immunochemotherapy with rituximab. Specific lymphoma involvement sites, especially the bones, bone marrow, and central nervous system, were identified as independent adverse prognostic factors. A high prevalence of non-germinal center B-cell (non-GCB) phenotype and myeloid differentiation primary response 88 (MYD88)/CD79B mutations were noted in lymphomas affecting the breasts, skin, uterus, and immune-privileged sites. Conversely, the thyroid and gastrointestinal tract showed a low occurrence of non-GCB phenotype. Remarkably, patients with multiple ENIs exhibited a high frequency of MYD88, tet methylcytosine dioxygenase 2 (TET2), CREB binding protein (CREBBP) mutations, increased MYD88^L265P and CD79B mutation (MCD)-like subtypes, and poor prognosis. Genetic subtype-guided immunochemotherapy showed good efficacy in subgroup analyses after propensity score matching with 5-year OS and progression-free survival rates of 85.0% (95% CI, 80.6%-89.5%) and 72.1% (95% CI, 67.3%-76.7%).</p><p><strong>Conclusions: </strong>In the rituximab era, this large-scale retrospective analysis from Asia confirmed the poor prognosis of DLBCL with multiple ENIs and underscored the efficacy of genetic subtype-guided immunochemotherapy in treating extranodal DLBCL.</p>","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":" ","pages":""},"PeriodicalIF":20.1,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ascites of patients with solid tumors shows distinct inflammatory patterns.","authors":"Julia M Berger, Martin Korpan, Carina Zierfuss, Katharina Syböck, Erwin Tomasich, Andreas Kienzle, Maria Koenig, Markus Kleinberger, Lynn Gottmann, Birgit Fendl, Cihan Ay, Johannes Pammer, Catharina Müller, Rudolf Oehler, Lorenz Balcar, Thomas Reiberger, Elisabeth S Bergen, Barbara Niederdorfer, Matthias Preusser, Anna S Berghoff","doi":"10.1002/cac2.70031","DOIUrl":"https://doi.org/10.1002/cac2.70031","url":null,"abstract":"","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":" ","pages":""},"PeriodicalIF":20.1,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143981511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Semaglutide impairs bioavailability of alectinib: a note of warning based on a cross-over pharmacokinetic drug-drug interaction study.","authors":"Niels Heersche, Daan A C Lanser, Esther Oomen-de Hoop, Attila Içli, Peter de Bruijn, Marthe S Paats, Elisabeth F C van Rossum, Stijn L W Koolen, Ron H N van Schaik, Anne-Marie C Dingemans, G D Marijn Veerman, Ron H J Mathijssen","doi":"10.1002/cac2.70030","DOIUrl":"https://doi.org/10.1002/cac2.70030","url":null,"abstract":"","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":" ","pages":""},"PeriodicalIF":20.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143981512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neutrophils in cancer: At the crucial crossroads of anti-tumor and pro-tumor.","authors":"Wenpeng Cai, Tao Fan, Chu Xiao, Ziqin Deng, Yixiao Liu, Chunxiang Li, Jie He","doi":"10.1002/cac2.70027","DOIUrl":"https://doi.org/10.1002/cac2.70027","url":null,"abstract":"<p><p>Neutrophils are important components of the immune system and play a key role in defending against pathogenic infections and responding to inflammatory cues, including cancer. Their dysregulation indicates potential disease risk factors. However, their functional importance in disease progression has often been underestimated due to their short half-life, especially as there is limited information on the role of intratumoral neutrophils. Recent studies on their prominent role in cancer have led to a paradigm shift in our understanding of the functional diversity of neutrophils. These studies highlight that neutrophils have emerged as key components of the tumor microenvironment, where they can play a dual role in promoting and suppressing cancer. Moreover, several approaches to therapeutically target neutrophils have emerged, and clinical trials are investigating their efficacy. In this review, we discussed the involvement of neutrophils in cancer initiation and progression. We summarized recent advances in therapeutic strategies targeting neutrophils and, most importantly, suggested future research directions that could facilitate the manipulation of neutrophils for therapeutic purposes in cancer patients.</p>","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":" ","pages":""},"PeriodicalIF":20.1,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143989948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk of colorectal cancer and cancer-related mortality in type 2 diabetes patients treated with metformin, SGLT-2 inhibitors, or their combination.","authors":"Xianhua Mao, Ka-Shing Cheung, Jing-Tong Tan, Lung-Yi Mak, Chi-Ho Lee, Ho Ming Cheng, Rex Wan-Hin Hui, Esther Wai Yin Chan, Philip Leung-Ho Yu, Man-Fung Yuen, Wai K Leung, Wai-Kay Seto","doi":"10.1002/cac2.70028","DOIUrl":"https://doi.org/10.1002/cac2.70028","url":null,"abstract":"","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":" ","pages":""},"PeriodicalIF":20.1,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143977256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel molecular mechanisms of immune evasion in hepatocellular carcinoma: NSUN2-mediated increase of SOAT2 RNA methylation.","authors":"Jinhua Jiang, Feng Liu, Dan Cui, Caixia Xu, Jiachang Chi, Tinghua Yan, Fang Guo","doi":"10.1002/cac2.70023","DOIUrl":"https://doi.org/10.1002/cac2.70023","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) is a deadly malignancy known for its ability to evade immune surveillance. NOP2/Sun RNA methyltransferase family member 2 (NSUN2), an RNA methyltransferase involved in carcinogenesis, has been associated with immune evasion and energy metabolism reprogramming. This study aimed to examine the molecular mechanisms underlying the involvement of NSUN2 in immune evasion and metabolic reprogramming of HCC.</p><p><strong>Methods: </strong>Single-cell transcriptomic sequencing was applied to examine cellular composition changes, particularly immune cell dynamics, in HCC and adjacent normal tissues. Bulk RNA-seq and proteomics identified key genes and proteins. Methylation sequencing and methylated RNA immunoprecipitation (MeRIP) were carried out to characterize the role of NSUN2 in 5-methylcytosine (m5C) modification of sterol O-acyltransferase 2 (SOAT2). Clinical samples from 30 HCC patients were analyzed using reverse transcription-quantitative polymerase chain reaction and Western blotting. Gene expression was manipulated using CRISPR/Cas9 and lentiviral vectors. In vitro co-culture models and metabolomics were used to study HCC cell-T cell interactions, energy metabolism, and immune evasion. Tumor growth in an orthotopic mouse model was monitored by bioluminescence imaging, with subsequent measurements of tumor weight, volume, and immunohistochemical staining.</p><p><strong>Results: </strong>Single-cell transcriptomic analysis identified a marked increase in malignant cells in HCC tissues. Cell communication analysis indicated that tumor cells might promote cancer progression by evading immune clearance. Multi-omics analyses identified NSUN2 as a key regulator in HCC development. MeRIP confirmed that NSUN2 facilitated the m5C modification of SOAT2. Analysis of human HCC tissue samples demonstrated pronounced upregulation of NSUN2 and SOAT2, along with elevated m5C levels in HCC tissues. In vitro experiments uncovered that NSUN2 augmented the reprogramming of energy metabolism and repressed the activity and cytotoxicity of CD8⁺ T cells, contributing to immune evasion. In vivo studies further substantiated the role of NSUN2 in fostering immune evasion and tumor formation of HCC by modulating the m5C modification of SOAT2.</p><p><strong>Conclusions: </strong>The findings highlight the critical role of NSUN2 in driving HCC progression through the regulation of m5C modification on SOAT2. These findings present potential molecular markers for HCC diagnosis and therapeutic targets for its treatment.</p>","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":" ","pages":""},"PeriodicalIF":20.1,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143977337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}