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Exploring Long Noncoding RNAs as Regulators of Tumor Ferroptosis: Advances and Challenges. 探索长链非编码rna作为肿瘤铁下垂调节因子:进展和挑战。
IF 5.7 2区 医学
Cancer Science Pub Date : 2025-04-02 DOI: 10.1111/cas.70074
Gang Li, Bing Wang, Lisha Ye, Guohua Wang
{"title":"Exploring Long Noncoding RNAs as Regulators of Tumor Ferroptosis: Advances and Challenges.","authors":"Gang Li, Bing Wang, Lisha Ye, Guohua Wang","doi":"10.1111/cas.70074","DOIUrl":"https://doi.org/10.1111/cas.70074","url":null,"abstract":"<p><p>Long noncoding RNAs (lncRNAs), a class of noncoding RNAs exceeding 200 nucleotides in length, play critical roles in regulating diverse biological processes and gene expression. Emerging evidence highlights their significant association with cancer occurrence, progression, prognosis, and therapeutic resistance, positioning lncRNAs as promising molecular targets for tumor detection and treatment. Ferroptosis, a regulated form of cell death characterized by the accumulation of iron-dependent lipid peroxides, has gained attention as a potential therapeutic strategy for cancer, complementing existing modalities such as surgery, chemotherapy, radiotherapy, hormone therapy, and targeted molecular therapy. Recent research demonstrates that lncRNAs modulate ferroptosis in solid tumors, thereby influencing tumor cell invasion, metastasis, and proliferation. Inducing ferroptosis has been shown to inhibit tumor growth, reduce chemoresistance, and enhance radiotherapy efficacy. This review explores recent advancements in understanding the role of lncRNAs in tumor ferroptosis, with a focus on their involvement in iron metabolism and their potential as therapeutic targets in cancer combination therapies.</p>","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143774816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Geographical Discrepancy in Medical Care Access Among Children, Adolescents, and Young Adults With Cancer in Japan, 2016-2019. 2016-2019 年日本儿童、青少年和青年癌症患者获得医疗服务的地域差异。
IF 5.7 2区 医学
Cancer Science Pub Date : 2025-04-02 DOI: 10.1111/cas.70069
Anna Tsutsui, Yoshitaka Murakami, Takako Fujimaki, Masayuki Endo, Yuko Ohno
{"title":"Geographical Discrepancy in Medical Care Access Among Children, Adolescents, and Young Adults With Cancer in Japan, 2016-2019.","authors":"Anna Tsutsui, Yoshitaka Murakami, Takako Fujimaki, Masayuki Endo, Yuko Ohno","doi":"10.1111/cas.70069","DOIUrl":"https://doi.org/10.1111/cas.70069","url":null,"abstract":"<p><p>In Japan, cancer control measures have been developed in specialized hospitals for children (0-14 years), and adolescents and young adults (15-39 years) patients with cancer. We investigated geographical discrepancies between residential addresses and cancer treatment hospitals in patients aged 0-39 in Japan between 2016 and 2019. Using Japan's National Population-Based Cancer Registry data (n = 99,968), we classified the cases into 10 diagnostic groups and four age groups: 0-14, 15-19, 20-29, and 30-39. Using five types of hospital groups, we examined the origin-destination relationships between patients' residences and hospitals at the prefecture and Secondary Medical Area (SMA) levels via cross-tabulation, summarizing the results using descriptive statistics and heat maps. Generalized Estimating Equation analysis was performed to investigate the factors associated with receiving treatment outside the residential prefecture based on individual data. The median percentage of patients receiving treatment within their residential prefecture was 81.82% or higher across age groups and hospital groups. At the SMA level, the percentage ranged from 0% to 57.00% (median)-minimum 0.0% and maximum 100.0%. Model analysis revealed that patients with retinoblastoma (adjusted risk ratio: 5.45) and those living in metropolitan (Tokyo: 3.73, Osaka: 2.00) and non-metropolitan and depopulated (1.67) areas were significantly more likely to travel outside their residential prefectures. These findings reveal that Japan faces geographical discrepancies in access to cancer care, particularly for specific cancer types and areas. These findings can inform targeted interventions to support equitable access to specialized cancer care for young Japanese patients.</p>","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143765506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Comparative Net Survival Analysis of Men and Women With Breast Cancer in Japan: A Population-Based Study. 日本男性和女性乳腺癌患者的比较净生存期分析:一项基于人群的研究。
IF 5.7 2区 医学
Cancer Science Pub Date : 2025-03-31 DOI: 10.1111/cas.70068
Daisy Sibale Mojoo, Isao Oze, Hiroshi Tsuge, Yukari Taniyama, Yuriko N Koyanagi, Sayaka Yamamoto, Megumi Hori, Kayo Nakata, Hiromi Sugiyama, Isao Miyashiro, Izumi Oki, Yoshikazu Nishino, Yuri Ito, Kota Katanoda, Akiko Shibata, Tomohiro Matsuda, Keitaro Matsuo, Hidemi Ito
{"title":"Comparative Net Survival Analysis of Men and Women With Breast Cancer in Japan: A Population-Based Study.","authors":"Daisy Sibale Mojoo, Isao Oze, Hiroshi Tsuge, Yukari Taniyama, Yuriko N Koyanagi, Sayaka Yamamoto, Megumi Hori, Kayo Nakata, Hiromi Sugiyama, Isao Miyashiro, Izumi Oki, Yoshikazu Nishino, Yuri Ito, Kota Katanoda, Akiko Shibata, Tomohiro Matsuda, Keitaro Matsuo, Hidemi Ito","doi":"10.1111/cas.70068","DOIUrl":"https://doi.org/10.1111/cas.70068","url":null,"abstract":"<p><p>While male breast cancer (MBC) remains a rare and understudied disease, comparatively little is known about its prognosis in contrast to female breast cancer (FBC). There is a paucity of large population-based studies comparing the prognosis of MBC patients to FBC patients in Japan. This study analyzed 181,540 breast cancer cases, 1058 (0.6%) males and 180,482 (99.4%) females, from 12 prefectures in Japan diagnosed between 1993 and 2011. Five- and ten-year net survival (NS) were estimated and stratified by sex, period, age, stage, and histological groups. Excess hazard ratios (EHR) were adjusted for period, age, stage, and histological group. Cochran's Q test was utilized to assess heterogeneity across these factors. The overall 5- and 10-year NS estimates for MBC patients were 90.7% (95% CI: 86.3%-93.7%) and 83.7% (95% CI: 72.2%-90.8%), respectively, while those for FBC patients were 88.3% (95% CI: 88.1%-88.5%) and 79.1% (95% CI: 78.7%-79.4%), respectively. The survival of MBC patients was comparable to that of FBC patients, with EHR of 0.88 [95% CI: 0.70-1.09] and 0.86 [95% CI: 0.69-1.07] for 5- and 10-year survival, respectively. Heterogeneity analysis revealed no significant sex-based differences in survival across these strata. This study offers a comprehensive analysis of breast cancer survival in Japanese men and women and enhances understanding of MBC prognosis relative to FBC.</p>","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143755424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Dual Targeting of Aurora-A and Bcl-xL Synergistically Reshapes the Immune Microenvironment and Induces Apoptosis in Breast Cancer. 双靶向Aurora-A和Bcl-xL协同重塑免疫微环境并诱导乳腺癌细胞凋亡
IF 5.7 2区 医学
Cancer Science Pub Date : 2025-03-30 DOI: 10.1111/cas.70072
Mingxue Liu, Jing Guo, Weiyong Liu, Zhenye Yang, Fazhi Yu
{"title":"Dual Targeting of Aurora-A and Bcl-xL Synergistically Reshapes the Immune Microenvironment and Induces Apoptosis in Breast Cancer.","authors":"Mingxue Liu, Jing Guo, Weiyong Liu, Zhenye Yang, Fazhi Yu","doi":"10.1111/cas.70072","DOIUrl":"https://doi.org/10.1111/cas.70072","url":null,"abstract":"<p><p>The Aurora-A kinase inhibitor MLN8237 has shown efficacy in clinical trials for advanced breast cancer; however, its use as a monotherapy is limited by significant side effects and modest efficacy. Therefore, combining MLN8237 with other agents at lower doses may provide a viable alternative. In this study, we evaluated the combination of MLN8237 with the BH3 mimetic ABT263 for the treatment of triple-negative breast cancer (TNBC). We found that this combination significantly suppressed tumor growth and metastasis in immunocompetent syngeneic mouse models, whereas its efficacy was attenuated in immunodeficient xenograft models. Mechanistic studies revealed that the combination enhanced anti-tumor immunity by increasing the presence of CD8<sup>+</sup> T cells and NK cells, while reducing the number of immunosuppressive cells in the tumor microenvironment. This shift resulted in elevated levels of IFN-γ and granzyme B, which activated the extrinsic apoptotic pathways in cancer cells. Notably, the combination treatment did not affect tumor cell proliferation but promoted apoptosis with minimal toxicity. Furthermore, the synergistic effect of MLN8237 and ABT263 in inducing intrinsic apoptosis was primarily driven by the inhibition of the AKT-Mcl-1 and Bcl-xL survival pathways in cultured tumor cells. Together, these findings support the MLN8237-ABT263 combination as an effective treatment strategy for TNBC, promoting both immune-mediated extrinsic apoptosis and inactivation of Bcl-xL/Mcl-1-dependent intrinsic anti-apoptotic pathways.</p>","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143755425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Real-World Data Analysis of Genomic Alterations Detected by a Dual DNA-RNA Comprehensive Genomic Profiling Test. 双DNA-RNA综合基因组分析测试检测到的基因组改变的真实世界数据分析。
IF 5.7 2区 医学
Cancer Science Pub Date : 2025-03-26 DOI: 10.1111/cas.70071
Kousuke Watanabe, Miho Ogawa, Aya Shinozaki-Ushiku, Shuichi Tsutsumi, Kenji Tatsuno, Hiroyuki Aburatani, Hidenori Kage, Katsutoshi Oda
{"title":"Real-World Data Analysis of Genomic Alterations Detected by a Dual DNA-RNA Comprehensive Genomic Profiling Test.","authors":"Kousuke Watanabe, Miho Ogawa, Aya Shinozaki-Ushiku, Shuichi Tsutsumi, Kenji Tatsuno, Hiroyuki Aburatani, Hidenori Kage, Katsutoshi Oda","doi":"10.1111/cas.70071","DOIUrl":"https://doi.org/10.1111/cas.70071","url":null,"abstract":"<p><p>GenMineTOP, the first dual DNA-RNA comprehensive genomic profiling (CGP) test in Japan, was approved for reimbursement in 2023. To evaluate its clinical utility, we analyzed 1356 cases from the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database. Oncogenic genomic alterations were identified in 91.5% of cases. Somatic mutations were the most prevalent, followed by amplifications and fusion/exon skipping events. The DNA panel, covering 737 genes, detected not only alterations relevant to therapeutic decisions but also those providing insights into tumor biology. Among the latter, frequently observed examples included mutations in KMT2C (n = 28) and ARID1B (n = 24), and amplifications in GLI1 (n = 14) and YAP1 (n = 10), which are not included in other CGP tests approved in Japan. The RNA panel identified 105 fusion events, including 11 NTRK fusions (0.8%), of which five were NTRK3 fusions: two with the well-known ETV6-NTRK3 fusion and three with non-ETV6 partners. Forty-nine of these fusions were diagnostically significant, highlighting the utility of the RNA panel. Amplification-RNA expression analyses revealed strong correlations for MDM2, CDK4, EGFR, and ERBB2. In contrast, weaker correlations observed for MYC and FGFR1 highlighted the need for careful interpretation of amplification in these genes. Cancer type significantly influenced RNA expression, with KIT and TERT mutations linked to increased expression and significant overexpression observed in ALK, FGFR3, NTRK1, NTRK3, and RET fusions. In summary, this study demonstrated the real-world clinical utility of the dual DNA-RNA CGP test and provided a valuable resource for interpreting RNA expressions.</p>","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Features of HLA-A*02 in Identifying Eligible Patients for Tecelra TCR-T Therapy. HLA-A*02在确定Tecelra TCR-T治疗患者中的特征
IF 5.7 2区 医学
Cancer Science Pub Date : 2025-03-13 DOI: 10.1111/cas.70048
Min Yang, Peiluan Zhong, Huifang Jiao, Pengcheng Wei
{"title":"Features of HLA-A*02 in Identifying Eligible Patients for Tecelra TCR-T Therapy.","authors":"Min Yang, Peiluan Zhong, Huifang Jiao, Pengcheng Wei","doi":"10.1111/cas.70048","DOIUrl":"https://doi.org/10.1111/cas.70048","url":null,"abstract":"<p><p>This study investigates the molecular mechanisms behind HLA-A*02 subtypes' differential responses to Tecelra, a TCR-engineered T-cell therapy targeting MAGE-A4. Using computational tools, the study identifies specific HLA-A*02 alleles, such as HLA-A*02:07, HLA-A*02:05, and others, with low affinity for the GV10 peptide or a risk of inducing alloreactivity. These findings provide insights into patient selection for Tecelra therapy, suggesting exclusion criteria for certain HLA-A*02 subtypes to optimize treatment efficacy and minimize adverse reactions.</p>","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143626493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Targeting RNA Polymerase I in Ewing Sarcoma Treatment. 靶向RNA聚合酶I治疗尤文氏肉瘤
IF 5.7 2区 医学
Cancer Science Pub Date : 2025-03-12 DOI: 10.1111/cas.70047
Alexis Bruce, Gavin Anchondo, Rebekah Carter, Sergio Guerrero Pacheco, Hema Sri Kambala, Elizabeth Cortez, Kyra Parker, Le Su
{"title":"Targeting RNA Polymerase I in Ewing Sarcoma Treatment.","authors":"Alexis Bruce, Gavin Anchondo, Rebekah Carter, Sergio Guerrero Pacheco, Hema Sri Kambala, Elizabeth Cortez, Kyra Parker, Le Su","doi":"10.1111/cas.70047","DOIUrl":"https://doi.org/10.1111/cas.70047","url":null,"abstract":"<p><p>Pharmacologic inhibition of RNA polymerase I activity represents a new therapeutic approach for Ewing sarcoma. This is the first time key components of the ribosome biogenesis pathway have been linked to Ewing sarcoma biology.</p>","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143606941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Time Lag Associated With the Reclassification of Germline BRCA Variants' Pathogenicity Is Critical for Cancer Patients. 与种系BRCA变异致病性重新分类相关的时间滞后对癌症患者至关重要。
IF 5.7 2区 医学
Cancer Science Pub Date : 2025-03-04 DOI: 10.1111/cas.70040
Tomomi Hayashi, Hiroyuki Matsubayashi, Yoshimi Kiyozumi
{"title":"The Time Lag Associated With the Reclassification of Germline BRCA Variants' Pathogenicity Is Critical for Cancer Patients.","authors":"Tomomi Hayashi, Hiroyuki Matsubayashi, Yoshimi Kiyozumi","doi":"10.1111/cas.70040","DOIUrl":"https://doi.org/10.1111/cas.70040","url":null,"abstract":"<p><p>The period for reclassifying the variants' pathogenicity is too long for patients with advanced or recurrent cancers with variants of uncertain significance that can be objectively re-evaluated to be (likely) pathogenic according to accumulated evidence. At present, we have three breast cancer patients with the germline variant BRCA2 c.7847C>T, which was genetically evaluated to be likely pathogenic by the paper in Cancer Science.</p>","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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