Cancer Science最新文献

{"title":"Tumor-Associated Macrophage-Derived CXCL1 Promotes Endometrial Cancer Progression Through the CXCR2/NF-κB Pathway","authors":"Ruiqi Xia,&nbsp;Dingtian Qi,&nbsp;Boshu Ji,&nbsp;Yisheng Dai,&nbsp;Xianchao Kong","doi":"10.1111/cas.70324","DOIUrl":"10.1111/cas.70324","url":null,"abstract":"<p>Advanced-stage and metastatic endometrial cancer (EC) are characterized by markedly poor survival outcomes, necessitating a deeper understanding of the mechanisms driving disease advancement. Tumor-associated macrophages (TAMs), particularly the M2 subtype, are instrumental in remodeling the tumor microenvironment and promoting EC proliferation, migration, and metastasis. However, the specific mediators responsible for TAM-driven EC progression remain inadequately elucidated. In this study, we investigated the role of the C–X–C motif chemokine ligand 1 (CXCL1) and its receptor, chemokine receptor 2 (CXCR2), in TAM-induced EC progression. CXCR2, as the primary receptor for CXCL1, activates the NF-κB signaling pathway upon binding, thereby mediating the epithelial–mesenchymal transition process in EC cells and enhancing metastatic potential. This mechanism can be effectively inhibited by silencing CXCR2 or by employing the NF-κB inhibitor BAY 11-7082. Neutralizing CXCL1 markedly diminished the proliferative and migratory burdens imposed by TAMs on EC in subcutaneous xenograft EC models. Additionally, in EC tissue samples, CXCL1 and CXCR2 expression, as well as the extent of macrophage infiltration, exhibited a significant positive relationship with disease progression, suggesting an unfavorable prognosis. In conclusion, targeting the CXCL1/CXCR2 axis is a potential therapeutic approach for EC treatment.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"117 4","pages":"1026-1042"},"PeriodicalIF":4.3,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13045360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145994402","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":"ZNF844 Suppresses Invasion and Metastasis in Nasopharyngeal Carcinoma by Inhibiting the PI3K-AKT Signaling Pathway","authors":"Jinping Xu,&nbsp;Cancan Chen,&nbsp;Bin Zhang,&nbsp;Shufang Liao,&nbsp;Yunyan Mo,&nbsp;Rongjun Zhang,&nbsp;Xiangyun Kong,&nbsp;Wei Jiang","doi":"10.1111/cas.70339","DOIUrl":"10.1111/cas.70339","url":null,"abstract":"<p>Epigenetic regulation plays a crucial role in the development of nasopharyngeal carcinoma (NPC). However, the epigenetic mechanisms underlying NPC recurrence and metastasis remain poorly understood. This study aimed to investigate and identify a novel molecular target with prognostic relevance in NPC. The methylation status of zinc finger protein 844 (<i>ZNF844</i>) was assessed in NPC tissues and cell lines using bisulfite pyrosequencing. <i>ZNF844</i> expression levels in NPC cell lines and clinical specimens were analyzed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting. Stable NPC cell lines with <i>ZNF844</i> overexpression or knockdown were established to evaluate its biological functions both in vitro and in vivo. RNA sequencing was performed to identify downstream targets of <i>ZNF844</i>, followed by validation using qRT-PCR and Western blotting. We found that <i>ZNF844</i> expression was significantly downregulated in NPC tissues and cell lines, correlating with hypermethylation of its promoter region. Treatment with the DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine (DAC) restored <i>ZNF844</i> mRNA expression. <i>ZNF844</i> overexpression suppressed NPC cell invasion and metastasis, whereas its silencing had the opposite effect. In xenograft models, <i>ZNF844</i> overexpression reduced metastatic burden. <i>ZNF844</i> inhibited the PI3K-AKT signaling pathway, thereby suppressing NPC cell invasiveness. Clinically, high <i>ZNF844</i> expression was associated with improved overall survival and distant metastasis-free survival. <i>ZNF844</i> inhibits the invasive and metastatic capabilities of nasopharyngeal carcinoma by modulating the PI3K–AKT signaling pathway. These inhibitory effects can be partially or completely reversed by treatment with SC79. It may serve as a promising therapeutic target and prognostic biomarker for NPC.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"117 4","pages":"943-957"},"PeriodicalIF":4.3,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13045358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146158899","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":"Analysis of Peripheral T Cell Profiling and Plasma Proteomics in Advanced NSCLC Patients Treated With Atezolizumab","authors":"Atsuto Mouri,&nbsp;Hiroshi Kagamu,&nbsp;Koji Tamada,&nbsp;Makoto Nishio,&nbsp;Hiroaki Akamatsu,&nbsp;Yasushi Goto,&nbsp;Hidetoshi Hayashi,&nbsp;Satoru Miura,&nbsp;Akihiko Gemma,&nbsp;Ichiro Yoshino,&nbsp;Toshihiro Misumi,&nbsp;Ryota Saito,&nbsp;Noriko Yanagitani,&nbsp;Fujita Masaki,&nbsp;Hiroshi Nokihara,&nbsp;Kazumi Nishino,&nbsp;Masahiro Seike,&nbsp;Tetsunari Hase,&nbsp;Osamu Hataji,&nbsp;Hiroaki Takeoka,&nbsp;Yosuke Kawashima,&nbsp;Hirotaka Kuroki,&nbsp;Masamichi Sugimoto,&nbsp;Hiroshi Kuriki,&nbsp;Tetsuya Mitsudomi","doi":"10.1111/cas.70310","DOIUrl":"10.1111/cas.70310","url":null,"abstract":"<p>We investigated immunologic biomarkers that predict outcomes of patients with previously treated metastatic non-small cell lung cancer who were enrolled in the J-TAIL study, a prospective, observational study of atezolizumab monotherapy. Of 262 patients participating in the J-TAIL exploratory study, peripheral blood mononuclear cells were obtained from 51 patients and analyzed by T-cell fractionation analysis using Helios mass cytometry and serum proteomics analysis. Following treatment with atezolizumab, an increase in programmed cell death-1 (PD-1)-expressing CD8 and CD4 T-cell populations was observed. A more pronounced increase in PD-1 expression was seen in T cells from patients whose progression-free survival (PFS) was 100 days or longer compared with those with shorter PFS. The proximity extension assay, which is highly sensitive multiplex analysis technology that combines antibody-based affinity assays with next-generation sequencing, showed a significant increase in FOXO1, possibly in response to precursor-exhausted T-cell population activation. Immune-related adverse events were associated with a high percentage of PD-1-positive cells on effector memory CD8 T cells, which was thought to be accompanied by extremely high CD8 T-cell activation. Further analysis distinguished poor prognosis populations with significant differences in CD62L_high Th7R and CXCR3⁺ component of Th7R (CXCR3⁺ Th7R) within the population with PFS &lt; 50 days. Patients with low Th7R or CXCR3⁺ Th7R percentages prior to atezolizumab treatment had significantly poorer overall survival. These findings provide valuable insights regarding T-cell kinetics and biomarkers in atezolizumab therapy and may offer promising directions for future research.</p><p><b>Trial Registration:</b> UMIN Clinical Trials Registry: UMIN000033133 and UMIN000035567; ClinicalTrials.gov: NCT03645330</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"117 4","pages":"904-916"},"PeriodicalIF":4.3,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13045310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146108112","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":"Therapeutic Strategies to Overcome Payload Resistance of Trastuzumab Deruxtecan in HER2-Positive Cancers","authors":"Yuya Murase,&nbsp;Shigeki Nanjo,&nbsp;Sachiko Arai,&nbsp;Sota Kondo,&nbsp;Hayato Koba,&nbsp;Yifeng Liu,&nbsp;Koji Fukuda,&nbsp;Shigeki Sato,&nbsp;Jun Kinoshita,&nbsp;Noriyuki Inaki,&nbsp;Tsukasa Ueda,&nbsp;Shunichi Nomura,&nbsp;Yuichi Tambo,&nbsp;Takahiro Shimizu,&nbsp;Masafumi Horie,&nbsp;Daichi Maeda,&nbsp;Richard W. Wong,&nbsp;Kazuyoshi Hosomichi,&nbsp;Takafumi Kobayashi,&nbsp;Satoshi Watanabe,&nbsp;Kenta Yamamura,&nbsp;Noriyuki Ohkura,&nbsp;Miki Abo,&nbsp;Seiji Yano","doi":"10.1111/cas.70319","DOIUrl":"10.1111/cas.70319","url":null,"abstract":"<p>Antibody–drug conjugates (ADCs) are emerging as a promising class of targeted cancer therapy. Trastuzumab deruxtecan (T-DXd), a human epidermal growth factor receptor 2 (HER2)-directed ADC, has demonstrated clinical efficacy in HER2-positive gastric and breast cancers, as well as in HER2-mutant non-small cell lung cancer. However, the development of acquired resistance limits their long-term efficacy. To elucidate the resistance mechanism, we established T-DXd-resistant cell lines derived from HER2-amplified gastric xenografts (N87 acquired resistance [AR]) and leptomeningeal carcinomatosis (Calu-3 AR) lung cancer cells. N87 AR cells exhibited cross-resistance to T-DXd, payload DXd, and topoisomerase I inhibitor SN-38 despite preserved HER2 expression and intact drug internalization. As payload resistance-related molecules, ATP-binding cassette (ABC) transporter ABCG2 and ABCB1 were markedly upregulated in N87 AR and Calu-3 cells, respectively. Inhibition of ABCG2 and ABCB1 in N87 AR and Calu-3 cells, respectively, through siRNA-mediated knockdown restored T-DXd sensitivity in both models. As a strategy to overcome resistance, pharmacological inhibitors of ABCG2 and ABCB1 restored the T-DXd sensitivity of N87 AR and Calu-3 cells, respectively. Moreover, BB-1701, a novel HER2-ADC containing eribulin as a payload, to which N87 AR cells are sensitive, exhibited antitumor effects in N87 AR cells in vitro and in vivo. These findings indicate that ABC transporter-mediated drug efflux is an important mechanism underlying T-DXd resistance in HER2-positive gastric and lung cancer models. Furthermore, our study suggests that both targeting drug efflux pathways and utilizing alternative payloads may be effective strategies for overcoming T-DXd resistance in HER2-positive gastric and lung cancers.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"117 4","pages":"996-1009"},"PeriodicalIF":4.3,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13045244/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145994386","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":"Pembrolizumab for Early-Stage Triple-Negative Breast Cancer: KEYNOTE-522 Japan Subgroup Analysis","authors":"Masato Takahashi,&nbsp;Hirofumi Mukai,&nbsp;Toshimi Takano,&nbsp;Koichiro Tsugawa,&nbsp;Kenichi Inoue,&nbsp;Mitsuya Itoh,&nbsp;Junichiro Watanabe,&nbsp;Yuko Tanabe,&nbsp;Naohito Yamamoto,&nbsp;Yasuo Miyoshi,&nbsp;Kenichi Watanabe,&nbsp;Toru Mukohara,&nbsp;Yibin Kong,&nbsp;Masashi Shimura,&nbsp;Francisco Beca,&nbsp;Peter Schmid,&nbsp;Hiroji Iwata","doi":"10.1111/cas.70307","DOIUrl":"10.1111/cas.70307","url":null,"abstract":"<p>The phase 3 KEYNOTE-522 study in high-risk early-stage triple-negative breast cancer (TNBC) showed significantly improved efficacy outcomes with neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab versus neoadjuvant chemotherapy alone. We present findings from the KEYNOTE-522 Japan subgroup. Eligible participants (aged ≥ 18 years) with untreated locally advanced TNBC (stage T1c N1–2 or T2–4 N0–2) were randomized 2:1 to neoadjuvant pembrolizumab 200 mg or placebo plus chemotherapy every 3 weeks for 8 cycles followed by surgery and adjuvant pembrolizumab or placebo for ≤ 9 cycles. Primary endpoints were pathologic complete response (pCR; ypT0/Tis ypN0) at the time of surgery and event-free survival (EFS). Of 76 participants enrolled in Japan, 45 were randomized to the pembrolizumab arm and 31 to the placebo arm. Median time from randomization to data cutoff (March 22, 2024) was 76.3 months. Twenty-four participants (53%) in the pembrolizumab arm and 15 (48%) in the placebo arm achieved pCR (between-treatment arm difference, 4.9%; 95% CI, −17.6% to 27.1%); findings were similar regardless of PD-L1 expression. Rates of EFS at 60 months were 84% and 73%, respectively (HR, 0.54; 95% CI, 0.20–1.50). Grade 3 or 4 treatment-related AEs occurred in 37 of 45 participants (82%) treated with pembrolizumab and 23 of 30 participants (77%) treated with placebo; there were no grade 5 AEs. In conclusion, neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab showed improved efficacy outcomes and manageable safety versus neoadjuvant chemotherapy alone in Japanese participants, supporting the use of this regimen in Japanese patients with high-risk early-stage TNBC.</p><p><b>Trial Registration:</b> The study (ClinicalTrials.gov, NCT03036488) was conducted in compliance with local and/or national regulations and International Council for Harmonization Good Clinical Practice guidelines and in accordance with the ethical principles originating from the Declaration of Helsinki</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"117 4","pages":"1106-1116"},"PeriodicalIF":4.3,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13045266/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145971470","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":"In-Tumor CRISPR-Cas9 Knockout Screening and Novel Therapy Development for Malignant Transformation of Ovarian Teratoma","authors":"Satoshi Tamauchi,&nbsp;Kosuke Yoshida,&nbsp;Wang Xinyuan,&nbsp;Atsushi Nakagawa,&nbsp;Akira Yokoi,&nbsp;Nobuhisa Yoshikawa,&nbsp;Kaoru Niimi,&nbsp;Yusuke Yamamoto,&nbsp;Hiroaki Kajiyama","doi":"10.1111/cas.70315","DOIUrl":"10.1111/cas.70315","url":null,"abstract":"<p>Malignant transformation of mature cystic teratoma (MTMCT) of the ovary is a rare but aggressive malignancy for which no standardized chemotherapy or effective targeted therapies currently exist. To identify therapeutic vulnerabilities in MTMCT, we performed a genome-wide CRISPR-Cas9 knockout screen using the MTMCT-derived NOSCC1 cell line. Two parallel selective pressures were applied: in vivo tumorigenicity in immunodeficient mice and cisplatin exposure in vitro. From this screen, 67 negatively selected genes were identified, among which SOD1 and NDUFB4 emerged as top candidates based on high basal expression levels and clinical relevance. Integration with spatial transcriptomic data from three independent MTMCT patient tumors further supported the prioritization of these targets. SOD1 was selected for further investigation due to the availability of known pharmacological inhibitors. Both siRNA-mediated knockdown and small-molecule inhibition of SOD1 using LCS-1 significantly suppressed MTMCT cell proliferation in vitro by inducing oxidative stress and impairing cell cycle progression. This antiproliferative effect was reversed by co-treatment with <i>N</i>-acetylcysteine, a reactive oxygen species scavenger. In vivo validation using patient-derived xenograft models demonstrated that oral administration of LCS-1 led to significant tumor growth suppression and increased expression of apoptotic and DNA damage markers, including cleaved caspase-3 and γH2AX. These findings establish SOD1 as a critical vulnerability in MTMCT and provide preclinical evidence supporting redox modulation as a therapeutic strategy for this highly chemoresistant and understudied ovarian cancer subtype. Our integrative approach combining functional genomics, spatial transcriptomics, and pharmacologic validation offers a framework for the discovery of novel targets in rare gynecologic malignancies.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"117 4","pages":"983-995"},"PeriodicalIF":4.3,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13045479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145967763","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":"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}