Cancer Science最新文献

{"title":"The Sparing Effect of Multibeam Ultra-High Dose-Rate Irradiation on Intestinal Tissue in Mice","authors":"Weiping Wang,&nbsp;Ziqi Zhou,&nbsp;Peng Wang,&nbsp;Fuquan Zhang,&nbsp;Jiaqi Qiu,&nbsp;Jian Wang,&nbsp;Ke Hu,&nbsp;Hao Zha","doi":"10.1111/cas.70340","DOIUrl":"10.1111/cas.70340","url":null,"abstract":"<p>The ultra-high dose-rate (UHDR) irradiation reduces normal tissue side effects compared to conventional dose-rate (CDR) irradiation—a phenomenon known as the FLASH effect. However, its clinical translation faces a critical barrier in achieving conformal dose distributions, as the brevity of single-beam UHDR delivery precludes gantry rotation. This necessitates understanding whether the FLASH tissue-sparing effect persists when the total dose is split into multiple beams with short intervals. In this study, mice received multibeam whole-abdominal irradiation using either UHDR or CDR beam. UHDR irradiation was delivered using electron beams at an average dose rate of ≥ 550 Gy/s. Multibeam regimens were delivered with 1-min intervals between each beam. Compared to CDR irradiation, multibeam UHDR irradiation significantly improved survival, as evidenced by higher rates following a regimen of 11 Gy in five beams. Similarly, body weight recovery was better with UHDR irradiation at 8 Gy in two beams than with CDR irradiation at 8 Gy, and intestinal crypt regeneration was greater with UHDR irradiation at 12 Gy in four beams than with CDR irradiation at 12 Gy. In conclusion, this study observed the maintenance of the intestinal FLASH effect in a murine model when irradiation was delivered in multiple beams within the tested per-beam dose range of 2.2–4 Gy. Registry and the Registration No. of the Study/Trial: Not Applicable.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"117 4","pages":"1072-1079"},"PeriodicalIF":4.3,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13045315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146158920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Applications of Phosphoproteomics: Illuminating Cancer Signaling and Enabling Rational Therapeutic Strategies","authors":"Hirokazu Shoji,&nbsp;Narikazu Boku,&nbsp;Jun Adachi","doi":"10.1111/cas.70323","DOIUrl":"10.1111/cas.70323","url":null,"abstract":"<p>Protein phosphorylation is a central post-translational modification regulating cellular signaling, frequently dysregulated in cancer. Mass spectrometry (MS)-based phosphoproteomics has emerged as a powerful approach to systematically profile phosphorylation events, thereby revealing aberrant kinase activity and therapeutic vulnerabilities that are not captured by genomic or transcriptomic analyses. Recent advances across the workflow—including optimized sample preparation and phosphopeptide enrichment, isotope- or label-free quantitative strategies, high-resolution mass spectrometry platforms, specialized algorithms for site identification and quantification, and integrative informatics analyses—have enabled the detection of tens of thousands of phosphorylation sites even from small clinical specimens. These developments have facilitated the characterization of signaling pathways across diverse cancer types, leading to the identification of targetable kinases and informing therapeutic strategies. In this review, we highlight studies that employed phosphoproteomic analyses of clinical specimens or patient-derived cancer cells to delineate signaling characteristics and to propose and validate therapeutic targets. Collectively, MS-based phosphoproteomics is poised to become a cornerstone of precision oncology. By enabling comprehensive and quantitative mapping of phosphorylation events, this technology allows mechanistic dissection of cancer signaling pathways and uncovers therapeutic vulnerabilities that may be exploited with targeted agents.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"117 4","pages":"885-895"},"PeriodicalIF":4.3,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13045499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146019965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IRF4 Enhances Radiosensitivity of Cervical Cancer by Inhibiting the PI3K/Akt/mTOR Pathway to Regulate Autophagy","authors":"Meihui Gao,&nbsp;Zhaolei Cui,&nbsp;Huachun Song,&nbsp;Yanhong Li,&nbsp;Anyang Li,&nbsp;Jianfeng Zheng,&nbsp;Linying Liu,&nbsp;Xuefen Lin,&nbsp;Wankai Fu,&nbsp;Yang Sun","doi":"10.1111/cas.70305","DOIUrl":"10.1111/cas.70305","url":null,"abstract":"<p>Interferon regulatory factor 4 (IRF4), a critical member of the IRF transcription factor family, harbors an elusive biological role in cervical cancer. Through immunohistochemical staining and immunoblotting, CCK-8 viability assays, EdU incorporation tests, clonogenic survival experiments, flow cytometric detection, transmission electron microscopy, immunofluorescence staining and heterotopic transplantation model, we discover that IRF4 expression was markedly decreased in cervical cancer tissues and cell lines compared to normal controls. Overexpression of IRF4 suppressed proliferation, migration, and invasion in both Siha and HeLa cells, while concurrently enhancing radiosensitivity. Mechanistically, IRF4 upregulated autophagy-related proteins (LC3, Beclin-1) and promoted autophagosome formation, while downregulating P62 by inhibiting the PI3K/Akt/mTOR pathway. In vivo studies demonstrated that IRF4 augmented the tumor response to radiation and further potentiated the effects when combined with rapamycin treatment, confirming its pivotal role in promoting radiosensitivity through PI3K/Akt/mTOR-mediated autophagy. IRF4 emerges as a critical regulator of cervical cancer progression via modulation of autophagy and influences the tumor's response to radiotherapy. It holds promise as a potential therapeutic target to enhance cervical cancer radiosensitivity.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"117 4","pages":"958-971"},"PeriodicalIF":4.3,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13045277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146004423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tafasitamab as Monotherapy or in Combination in Japanese Patients With B-Cell Non-Hodgkin Lymphoma: Results From the Phase 1b J-MIND Study","authors":"Koji Izutsu,&nbsp;Noriko Fukuhara,&nbsp;Junichiro Yuda,&nbsp;Youko Suehiro,&nbsp;Shigeru Kusumoto,&nbsp;Marie-Laure Casadebaig,&nbsp;Kazumi Suzukawa,&nbsp;Kentaro Fukushima","doi":"10.1111/cas.70306","DOIUrl":"10.1111/cas.70306","url":null,"abstract":"<p>We conducted a phase 1b study evaluating safety and tolerability of tafasitamab, a CD19-targeting immunotherapy, in Japanese patients with B-cell non-Hodgkin lymphoma (NHL). Eligible patients were ≥ 18 years old with relapsed/refractory (R/R) B-cell NHL (Group 1), R/R diffuse large B-cell lymphoma (DLBCL; Groups 3 and 4), or untreated DLBCL (Group 5). Patients received tafasitamab starting at 12 mg/kg qw (Group 1, <i>n</i> = 6), tafasitamab + lenalidomide starting at 25 mg qd for ≤ 12 cycles (Group 3, <i>n =</i> 6), tafasitamab + parsaclisib starting at 20 mg qd (Days 1–56) then 2.5 mg qd (Group 4, <i>n =</i> 6), or tafasitamab + lenalidomide combined with R-CHOP for ≤ 6 cycles (Group 5, <i>n =</i> 6). Primary objective was safety and tolerability of tafasitamab alone and in combination; exploratory objectives included efficacy. At data cutoff (August 31, 2023), 24 patients were treated. All patients experienced treatment-emergent adverse events (TEAEs). Two patients experienced a dose-limiting toxicity; liver disorder (grade 4) considered related to lenalidomide (Group 3, <i>n =</i> 1), and febrile neutropenia (grade 3) considered related to lenalidomide and R-CHOP (Group 5, <i>n =</i> 1). Most common TEAEs across groups were hematological and included neutropenia, leukopenia, thrombocytopenia, and anemia; most common non-hematological TEAEs included increased alanine aminotransferase, increased aspartate aminotransferase, diarrhea, nausea, constipation, and infusion-related reactions. No serious tafasitamab treatment-related or fatal TEAEs were observed. Results suggest tafasitamab alone or in combination demonstrates a manageable safety profile in Japanese patients with B-cell NHL. Preliminary efficacy results from the study are reported. However, results should be interpreted with caution due to the small sample size, with further studies warranted to confirm these findings.</p><p><b>Trial Registration:</b> NCT04661007; jRCT2031200357</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"117 4","pages":"1093-1105"},"PeriodicalIF":4.3,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13045400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146019920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and Validation of a Urinary Exosomal miRNA Diagnostic Panel for Early Detection of Esophageal Cancer","authors":"Tatsuro Murano,&nbsp;Hiroki Yamashita,&nbsp;Yuki Kano,&nbsp;Ken Takeuchi,&nbsp;Takayuki Amano,&nbsp;Takanobu Yoshimoto,&nbsp;Mayuko Otomo,&nbsp;Hisashi Fujiwara,&nbsp;Shin Namiki,&nbsp;Hiroki Yamaguchi,&nbsp;Yoriko Ando,&nbsp;Yumi Nishiyama,&nbsp;Mika Mizunuma,&nbsp;Yuki Ichikawa,&nbsp;Tomonori Yano","doi":"10.1111/cas.70298","DOIUrl":"10.1111/cas.70298","url":null,"abstract":"<p>Esophageal squamous cell carcinoma (ESCC) remains a leading cause of cancer-related mortality, with early detection being challenging. Although endoscopic screening can aid in diagnosis, its invasiveness and cost limit widespread compliance. To address this, we developed and validated a non-invasive diagnostic panel based on urinary exosomal microRNAs (miRNAs) for early ESCC detection. Urine samples were prospectively collected from ESCC patients and healthy controls across five institutions, and exosomal miRNA profiles were obtained using small RNA sequencing. A diagnostic panel was constructed using machine learning with recursive feature elimination in a proof-of-concept (POC) cohort comprising 99 ESCC and 93 control samples, and its performance was evaluated by five-fold cross-validation. This panel was subsequently tested in a blinded validation cohort of 50 ESCC and 61 control samples. In the POC cohort, the multi-miRNA panel achieved an area under the curve (AUC) of 0.90. In the validation cohort, the AUC was 0.85 (95% CI: 0.77–0.92), with 84% sensitivity and 66% specificity. The panel showed high sensitivity across disease stages—100% for Stage 0, 91% for Stage I, and 73% for Stages II–IV—and its performance was not significantly affected by sex, body mass index, alcohol use, or smoking. Furthermore, in early-stage cases, the diagnostic score significantly declined after treatment (<i>p</i> = 0.026). These findings suggest that the urinary exosomal miRNA panel may offer a practical screening approach for the early detection of ESCC.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"117 4","pages":"1080-1092"},"PeriodicalIF":4.3,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13045446/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146004414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"KRAB Zinc-Finger Protein ZNF205 Promotes Hepatocellular Carcinoma via p53 Pathway Repression","authors":"Xiaofen Huang,&nbsp;Yingchuan Yang,&nbsp;Yuan Ma,&nbsp;Wei Hao,&nbsp;Jingzhuo Jin,&nbsp;Yue Ding,&nbsp;Yiming Zhang,&nbsp;Xiuyuan Zhang,&nbsp;Xinli Li,&nbsp;Qin Song,&nbsp;Jiaqi Liu,&nbsp;Bingxin Liu,&nbsp;Yuanjun Zhai,&nbsp;Chunling Zhao,&nbsp;Jin Wu,&nbsp;Chunyan Tian","doi":"10.1111/cas.70337","DOIUrl":"10.1111/cas.70337","url":null,"abstract":"<p>The tumor suppressor p53 is frequently dysregulated in cancer, whereas the mechanisms underlying its functional impairment remain unclear. Our previously identified KRAB domain-containing zinc finger proteins (KZFPs) as key p53 regulators in tumorigenesis and progression, specific members and their cancer-relevant mechanistic roles require further characterization. Here, we identified ZNF205, an SQ/TQ motif-bearing KZFP, as a critical oncogenic regulator in HCC. The pan-cancer analysis related to revealed that ZNF205 is an unfavorable prognostic factor for p53 wild-type patients with hepatocellular carcinoma (HCC). ZNF205 interacts with p53 and significantly inhibits its transcriptional activity by impeding the binding of p53 to target genes. Overexpression and knockdown of ZNF205 increase and decrease the malignant phenotype of HCC cells in a p53-dependent manner both in vitro and in vivo, respectively. Our study unveils ZNF205 as a novel p53 regulator and establishes its pro-tumorigenic function in HCC. These results reveal a novel p53 dysregulation mechanism in HCC and expand known KZFP-mediated p53 inactivation pathways, nominating ZNF205 as a therapeutic target to restore p53 function in HCC.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"117 4","pages":"1057-1071"},"PeriodicalIF":4.3,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13045463/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146158910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IAP Antagonists Selectively Eliminate Therapy-Induced Senescent Cancer Cells via TNFα-Independent Apoptosis","authors":"Hiroaki Ochiiwa,&nbsp;Takeshi Wakasa,&nbsp;Yuki Kataoka,&nbsp;Koji Ando,&nbsp;Eiji Oki,&nbsp;Yoshihiko Maehara,&nbsp;Makoto Iimori,&nbsp;Hiroyuki Kitao","doi":"10.1111/cas.70329","DOIUrl":"10.1111/cas.70329","url":null,"abstract":"<p>Therapy-induced senescence (TIS) is a state in which cancer cells enter growth arrest following chemotherapy. TIS cancer cells influence the tumor microenvironment through their senescence-associated secretory phenotype and independently acquire stem-like properties, both of which contribute to increased aggressiveness and tumor relapse. Here, we show that AZD5582 and AT406, potent antagonists of cellular inhibitor of apoptosis proteins 1 and 2 (cIAP1 and cIAP2) and X-linked inhibitor of apoptosis protein (XIAP), selectively eliminated HCT116 and RKO cells that had undergone senescence following treatment with a chemotherapeutic agent such as trifluridine, camptothecin, or doxorubicin. This elimination occurred via apoptosis associated with caspase 8 activation. These TIS cancer cells produced and secreted tumor necrosis factor α (TNFα); however, the selective cytotoxicity of IAP antagonists toward TIS cells was unexpectedly largely TNFα-independent. Consistently, the same IAP antagonists sensitized cancer cells treated with nutlin-3a, which induces senescence without TNFα production. Depletion of both cIAP1 and XIAP recapitulated the selective cytotoxicity against both TIS and nutlin-3a-induced senescent cancer cells. At physiological concentrations, TNFα sensitized non-senescent, proliferating cancer cells, but not TIS and nutlin-3a-induced senescent cancer cells, to apoptosis in the presence of IAP antagonists. Collectively, these findings suggest that IAP antagonists could serve as effective concomitant agents to TIS-inducing chemotherapy that promotes TNFα secretion within tumors, functioning not only as TNFα-independent senolytics but also as potentiators of TNFα-mediated apoptosis in adjacent non-senescent, proliferating cancer cells.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"117 4","pages":"1043-1056"},"PeriodicalIF":4.3,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13045222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146054683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cancer-Specific Antihuman Podoplanin Antibody chLpMab-2f Exerts Antitumor Effects Against Pleural Mesothelioma","authors":"Aito Yoshida,&nbsp;Shinji Abe,&nbsp;Toshihiro Izumi,&nbsp;Satoshi Itakura,&nbsp;Keichiro Yamada,&nbsp;Takuya Wada,&nbsp;Takaaki Yamamoto,&nbsp;Chiemi Sato,&nbsp;Atsushi Mitsuhashi,&nbsp;Hirokazu Ogino,&nbsp;Seidai Sato,&nbsp;Tsutomu Shinohara,&nbsp;Masaki Hanibuchi,&nbsp;Mika K. Kaneko,&nbsp;Yukinari Kato,&nbsp;Yasuhiko Nishioka","doi":"10.1111/cas.70325","DOIUrl":"10.1111/cas.70325","url":null,"abstract":"<p>Pleural mesothelioma (PM) is a malignancy with a poor prognosis owing to its resistance to chemotherapy. To develop a novel treatment for PM, podoplanin (PDPN), a transmembrane glycoprotein, has attracted significant attention because it is highly expressed in PM and is used for its diagnosis. We previously reported that NZ-12, a human chimeric antihuman PDPN antibody, exhibits antitumor effects against human PM cells through antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Additionally, we developed a cancer-specific monoclonal antibody (CasMab) production technology and produced a mouse-human chimeric cancer-specific antihuman PDPN antibody, chLpMab-2, along with an afucosylated version, chLpMab-2f, to enhance ADCC activity. This study aimed to evaluate whether chLpMab-2f exhibits specific antitumor effects against PM in a preclinical model. We demonstrated that chLpMab-2f recognized the surface PDPN of human PM cell lines and human PM patient tissue but did not react with human normal tissues such as lung and kidney tissues. Furthermore, these antibodies exhibited ADCC and CDC activity against PDPN-positive PM cells while showing reduced toxicity toward non-malignant kidney-derived PDPN-positive cells, such as HEK-293FT. Additionally, chLpMab-2f demonstrated stronger ADCC activity through more efficient NK cell activation in comparison to chLpMab-2. Moreover, chLpMab-2f suppressed tumor progression in subcutaneously and intrathoracically transplanted human PM cells in mice. These findings suggest that PDPN-targeting immunotherapy with chLpMab-2f generated by CasMab technology could provide an effective treatment for PM with decreased toxicity toward normal tissues.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"117 4","pages":"917-928"},"PeriodicalIF":4.3,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13045471/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146012923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FB23-2 and Cisplatin Synergize to Inhibit Head and Neck Squamous Cell Carcinoma by Targeting the XPF/ERCC1 Complex","authors":"Yaoqi Jiang,&nbsp;Hongshi Cai,&nbsp;Yue Zhu,&nbsp;Jianfeng Liang,&nbsp;Hongyu Li,&nbsp;Fan Song,&nbsp;Ziyi Wang,&nbsp;Jinsong Hou","doi":"10.1111/cas.70322","DOIUrl":"10.1111/cas.70322","url":null,"abstract":"<p>Head and neck squamous cell carcinoma (HNSCC) is a highly aggressive malignancy with a poor prognosis, often necessitating multimodal treatment approaches. While cisplatin (CDDP) remains the first-line chemotherapeutic agent, treatment failure frequently occurs due to drug resistance. To address this challenge, the FTO inhibitor FB23-2 has emerged as a promising candidate to enhance therapeutic efficacy. Consequently, this study aims to evaluate the combined efficacy of CDDP and FB23-2 in HNSCC and investigate their synergistic mechanisms. Using CCK-8 assays, colony formation assays, and flow cytometry for proliferation and cell cycle analysis, we observed that the CDDP-FB23-2 combination synergistically suppressed HNSCC proliferation. This treatment induced S/G2 phase cell cycle arrest and subsequent mitotic catastrophe. We further validated these findings in vivo using 4NQO-induced HNSCC mouse models. Additionally, drug safety was assessed via H&amp;E staining of visceral organs, which revealed that a semi-combined regimen reduced treatment-related side effects. Mechanistic investigations involving immunofluorescence (IF), quantitative real-time PCR (qRT-PCR), co-immunoprecipitation (Co-IP), and western blot analyses demonstrated that FB23-2 potentiated CDDP-induced DNA damage while inhibiting DNA repair mechanisms, thereby promoting apoptotic cell death. Specifically, FB23-2 blocked the assembly and nuclear translocation of XPF/ERCC1 complexes in CDDP-treated cells, directly increasing cellular sensitivity to CDDP. Collectively, our findings demonstrate that FB23-2 enhances CDDP sensitivity in HNSCC by targeting the XPF/ERCC1 complex, providing a theoretical basis and experimental support for their clinical application in HNSCC treatment.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"117 4","pages":"1010-1025"},"PeriodicalIF":4.3,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13045221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146019922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Roles of TIF1β in Leukemic Stem Cell Through SETDB1-Dependent and Independent Mechanisms","authors":"Mariko Morii,&nbsp;Sho Kubota,&nbsp;Goro Sashida","doi":"10.1111/cas.70334","DOIUrl":"10.1111/cas.70334","url":null,"abstract":"<p>TIF1β/TRIM28/KAP1 has been recognized as a scaffold protein that partners with KRAB-ZFPs and heterochromatin complexes to enforce gene silencing. In embryonic and pluripotent stem cells, it maintains self-renewal by silencing endogenous retroelements through the establishment of heterochromatin. While these canonical functions have been extensively examined in embryonic stem (ES) cells, accumulating evidence also highlights its diverse contributions to cancer biology. We herein focused on the oncogenic role of TIF1β in leukemic progression, contrasting this with its physiological roles in hematopoietic stem cell maintenance, differentiation, and immune regulation, thereby providing a comparative perspective on H3K9 methyltransferase SETDB1-dependent and -independent mechanisms. TIF1β-mediated epigenetic plasticity was recently shown to establish a leukemic chromatin environment for promoting oncogenic transcriptional programs while repressing lineage-differentiation regulators, which drives leukemic progression in a context-dependent manner. This review summarizes the dual role of TIF1β as a chromatin modulator, functioning both as a canonical transcriptional co-repressor and as a context-dependent co-activator, and also discusses how these modalities cooperate to sustain leukemic stem cell programs.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"117 4","pages":"896-903"},"PeriodicalIF":4.3,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13045245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146067987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}