Cancer Science最新文献_第7页

TRIM59 Drives Bladder Cancer Progression Through E3 Ligase-Dependent K48-Linked Degradation of PTRF. TRIM59通过E3连接酶依赖的k48相关的PTRF降解驱动膀胱癌进展。

IF 4.3 2区医学

Cancer Science Pub Date : 2026-08-21 DOI: 10.1111/cas.70510

Junlin Gan, Xuesong Bai, Aijie Zhang, Fei Lin, Hang Tong, Tinghao Li, Ning Xu, Xinyuan Li, Zhou Yu, Hubin Yin

{"title":"TRIM59 Drives Bladder Cancer Progression Through E3 Ligase-Dependent K48-Linked Degradation of PTRF.","authors":"Junlin Gan, Xuesong Bai, Aijie Zhang, Fei Lin, Hang Tong, Tinghao Li, Ning Xu, Xinyuan Li, Zhou Yu, Hubin Yin","doi":"10.1111/cas.70510","DOIUrl":"https://doi.org/10.1111/cas.70510","url":null,"abstract":"Tripartite motif-containing 59 (TRIM59) is an E3 ubiquitin ligase implicated in multiple malignancies, but its role in bladder cancer (BLCA) remains incompletely understood. In this study, we identified TRIM59 as a clinically relevant oncogenic driver in BLCA through integrated transcriptomic, clinical, and functional analyses. TRIM59 was significantly upregulated in BLCA tissues and cell lines, and high TRIM59 expression was associated with advanced stage, higher grade, recurrence, and poor prognosis. Functionally, TRIM59 promoted BLCA proliferation, cell-cycle progression, migration, invasion, and metastatic colonization in vitro and in vivo. Mechanistically, TRIM59 directly interacted with PTRF/Cavin-1 and induced its RING domain-dependent K48-linked polyubiquitination and proteasomal degradation. Additional mutagenesis analyses identified K98, K122, K152, and K317 as major ubiquitination sites on PTRF. In contrast to the oncogenic role of TRIM59, PTRF was downregulated in BLCA and exhibited tumor-suppressive properties. PTRF restoration attenuated TRIM59-driven proliferation, invasion, and epithelial-mesenchymal transition, whereas PTRF depletion partially rescued the inhibitory effects of TRIM59 silencing. Further analyses showed that PTRF restrains AKT phosphorylation and suppresses MYC transcriptional activity, thereby limiting c-Myc-driven proliferative signaling. Collectively, these findings define a previously unrecognized TRIM59-PTRF-AKT/c-Myc axis that drives BLCA progression and highlight TRIM59 as a potential prognostic biomarker and therapeutic target.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13494489/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148800350","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}

引用次数: 0

Myofibroblast-Like CAFs in Metastatic Lymph Nodes Drive Tumor Stemness and Poor Prognosis in Head and Neck Cancer. 转移性淋巴结中的肌成纤维细胞样CAFs驱动肿瘤干性和头颈癌的不良预后。

IF 4.3 2区医学

Cancer Science Pub Date : 2026-08-20 DOI: 10.1111/cas.70511

Hiroyuki Hagiwara, Hideyuki Takahashi, Reika Kawabata-Iwakawa, Miho Uchida, Hiroe Tada, Toshiyuki Matsuyama, Masaomi Motegi, Yuichi Tomidokoro, Kazuaki Chikamatsu

{"title":"Myofibroblast-Like CAFs in Metastatic Lymph Nodes Drive Tumor Stemness and Poor Prognosis in Head and Neck Cancer.","authors":"Hiroyuki Hagiwara, Hideyuki Takahashi, Reika Kawabata-Iwakawa, Miho Uchida, Hiroe Tada, Toshiyuki Matsuyama, Masaomi Motegi, Yuichi Tomidokoro, Kazuaki Chikamatsu","doi":"10.1111/cas.70511","DOIUrl":"https://doi.org/10.1111/cas.70511","url":null,"abstract":"Lymph node (LN) metastasis is one of the major prognostic factors in head and neck squamous cell carcinoma (HNSCC), and treatment sensitivity often differs between primary tumors and metastatic LNs. Beyond tumor cell-intrinsic differences, heterogeneity of the tumor microenvironment may contribute to these discrepancies. We focused on cancer-associated fibroblasts (CAFs) and compared CAFs derived from primary tumors and corresponding LN metastases. Bulk tissue analysis showed higher expression of myofibroblast-related genes (ACTA2, MYL9, MYLK) and increased COMP expression in metastatic LNs. Thirteen paired CAFs were established and serially passaged. Compared with primary tumor-derived CAFs (PT-CAFs), metastatic LN-derived CAFs (LN-CAFs) exhibited reduced proliferative and migratory capacities, but enhanced collagen gel contraction, while promoting tumor cell-sphere formation and cancer stem cell marker expression. These findings support a myofibroblast-like phenotype in LN-CAFs. In line with this, PT-CAFs showed greater induction of myofibroblast-related genes in response to TGF-β, but not IL-6 stimulation, suggesting that LN-CAFs had already differentiated toward a myofibroblast-like phenotype. RNA sequencing of five paired CAFs confirmed a myofibroblastic transcriptional profile, with enrichment of fibrosis-related and malignant trait-associated pathways, including epithelial-mesenchymal transition (EMT), hypoxia, and p53 signaling. Finally, least absolute shrinkage and selection operator-based prognostic models validated in The Cancer Genome Atlas (TCGA) cohort using genes upregulated in LN-CAFs were significantly associated with worse progression-free survival and overall survival. These results demonstrate that CAF heterogeneity depends on tumor localization and is linked to therapeutic resistance and poor clinical outcomes in HNSCC.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13491124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148800324","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}

引用次数: 0

Defining Age to Screen and Real-World Effectiveness for Early-Onset Colorectal Cancer. 确定早发性结直肠癌筛查的年龄和实际效果。

IF 4.3 2区医学

Cancer Science Pub Date : 2026-08-20 DOI: 10.1111/cas.70505

Le Wang, Yu Qiu, Xuechen Chen, Weimiao Wu, Chen Zhu, Weiwei Chen, Tingting Pan, Dong Hang, Lingbin Du

引用次数: 0

Proportion of Screen-Detected Gastrointestinal Cancers From the National Cancer Registry in Japan. 来自日本国家癌症登记处的筛查发现的胃肠道癌症比例。

IF 4.3 2区医学

Cancer Science Pub Date : 2026-08-20 DOI: 10.1111/cas.70509

Ryuji Okamoto, Yukai Lu, Taisuke Ishii, Tomio Nakayama, Kensuke Shinmura, Tomonori Yano, Motoki Iwasaki

{"title":"Proportion of Screen-Detected Gastrointestinal Cancers From the National Cancer Registry in Japan.","authors":"Ryuji Okamoto, Yukai Lu, Taisuke Ishii, Tomio Nakayama, Kensuke Shinmura, Tomonori Yano, Motoki Iwasaki","doi":"10.1111/cas.70509","DOIUrl":"https://doi.org/10.1111/cas.70509","url":null,"abstract":"Historically, information on routes of diagnosis in cancer registration in Japan lacked reliability. The launch of the National Cancer Registry in 2016 produced a marked improvement in data accuracy. In this study, we aimed to estimate the proportion of screen-detected gastrointestinal cancers using the National Cancer Registry and to examine its correlation with cancer screening participation rates. We analyzed 2016-2020 National Cancer Registry data to identify screen-detected gastrointestinal cancers and assess the correlation between route of diagnosis and stage at diagnosis. Screening participation rates were extracted from the Comprehensive Survey of Living Conditions (CSLC) and the Report on Regional Public Health Services and Health Promotion Services via e-Stat, and their correlations with screen-detected cancer proportions were assessed using prefecture-level data. Screen-detected cancers accounted for 14.4% for esophageal cancer, 18.6% for gastric cancer, and 21.3% for colorectal cancer. Cancers detected through \"other routes (including symptomatic detection)\" accounted for 47.1%, 41.6%, and 45.1%, respectively. Screen-detected cases more frequently presented as intraepithelial or localized disease. In gastric and colorectal cancer, positive correlations were observed between the proportions of screen-detected cancers and screening participation rates; for example, correlation coefficients based on the 2019 CSLC were 0.61 for gastric cancer and 0.71 for colorectal cancer. Screen-detected gastrointestinal cancers accounted for roughly 20% of all detected routes. Higher screening rates were correlated with higher proportions of screen-detected cancers. These findings suggest that the proportion of screen-detected cancers may serve as an indicator of screening program quality.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13491109/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148800341","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}

引用次数: 0

Genetic Engineering of Tumor-Infiltrating Lymphocytes (TIL) via a T-Editor Platform to Enhance Anti-Tumor Activity. 利用T-Editor平台对肿瘤浸润淋巴细胞（TIL）进行基因工程以增强抗肿瘤活性。

IF 4.3 2区医学

Cancer Science Pub Date : 2026-08-19 DOI: 10.1111/cas.70502

Fenge Li, Xuejiao Ma, Yongming Xue, Jilong Yang, Ruijing Wang, Xiang Li, Chao Zhang, Wenhan Lu, Mei Liu, Yue Xu, Xinyi Wang, Shengnan Wu, Ning Kang, Chunhua Ma

{"title":"Genetic Engineering of Tumor-Infiltrating Lymphocytes (TIL) via a T-Editor Platform to Enhance Anti-Tumor Activity.","authors":"Fenge Li, Xuejiao Ma, Yongming Xue, Jilong Yang, Ruijing Wang, Xiang Li, Chao Zhang, Wenhan Lu, Mei Liu, Yue Xu, Xinyi Wang, Shengnan Wu, Ning Kang, Chunhua Ma","doi":"10.1111/cas.70502","DOIUrl":"https://doi.org/10.1111/cas.70502","url":null,"abstract":"Tumor-infiltrating lymphocytes (TIL) therapy has demonstrated clinical potential in malignancies. However, limited understanding of why only a subset of patients respond to TIL therapy, coupled with the lack of simple and efficient methods to genetically engineer fragile TIL, has hindered efforts to enhance TIL efficacy through genetic modification. A T-Editor platform enabling rapid and efficient CRISPR-mediated gene editing in TIL was developed and optimized. To minimize the risk of chromosomal translocations associated with Cas9-induced double-strand breaks (DSBs), single-guide RNAs (sgRNAs) were designed for cytosine base editing (CBE). The expansion capacity, phenotypic profile, cytokine production, and in vitro cytolytic activity of base-edited TIL were compared with those of Cas9-KO TIL. In vivo efficacy was assessed using patient-derived xenograft (PDX) mouse models. The T-Editor platform was optimized for TIL gene editing by refining stimulation conditions, electroporation parameters, and CRISPR/Cas9 reagent dosing. FAM84B emerged as the top candidate, with its knockout resulting in the most pronounced enhancement of TIL cytolytic activity. CBE-mediated C·G-to-T·A conversion in the FAM84B exon achieved high editing efficiency with minimal insertion-deletion (indel) events. Base-edited TIL exhibited comparable expansion, phenotype, cytokine production, and in vitro cytolytic activity relative to Cas9-KO TIL. Compared with non-engineered control TIL, FAM84B-edited TIL displayed an increased CD62L+ memory subset, enhanced effector function and cytolytic activity, and improved in vivo antitumor efficacy. In conclusion, the T-Editor platform enables rapid and efficient CRISPR-mediated gene editing for engineering TIL to enhance its therapeutic potency. FAM84B may represent a novel potential target for improving TIL-mediated antitumor activity.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13488124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148800271","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}

引用次数: 0

Ionizing Radiation and Ultraviolet Light Irradiation-Associated DNA Damage Increasing Genomic Instability Risk. 电离辐射和紫外线照射相关的DNA损伤增加基因组不稳定风险。

IF 4.3 2区医学

Cancer Science Pub Date : 2026-08-14 DOI: 10.1111/cas.70500

Ken-Ichi Yoshioka, Yusuke Matsuno, Rika Kusumoto-Matsuo

引用次数: 0

Mitochondrial Morphology Dynamics Remodel Metabolism and Affect TKI Sensitivity in EGFR-Mutated Lung Cancer. egfr突变肺癌的线粒体形态动力学重塑代谢并影响TKI敏感性。

IF 4.3 2区医学

Cancer Science Pub Date : 2026-08-13 DOI: 10.1111/cas.70488

Yu Zhao, Yuqiang Liu, Mingxuan Xie, Zhiming Ye, Hong Huang, Maojin Yao, Feng Zhou, Jianzhu Zhao, Jun Tang

{"title":"Mitochondrial Morphology Dynamics Remodel Metabolism and Affect TKI Sensitivity in EGFR-Mutated Lung Cancer.","authors":"Yu Zhao, Yuqiang Liu, Mingxuan Xie, Zhiming Ye, Hong Huang, Maojin Yao, Feng Zhou, Jianzhu Zhao, Jun Tang","doi":"10.1111/cas.70488","DOIUrl":"10.1111/cas.70488","url":null,"abstract":"EGFR-mutant non-small cell lung cancer patients often exhibit resistance to TKI therapy. This treatment resistance is a key factor affecting the efficacy of TKIs and a major bottleneck in cancer treatment. The potential underlying cause may be closely related to tumor cell metabolic reprogramming. In this study, we established an EGFR-mutant lung cancer mouse model, isolating and culturing tumor primary cells to explore the cellular and molecular mechanisms of EGFR-mutant lung cancer. Using techniques such as super-resolution microscopy and RNA-seq, we qualitatively and quantitatively analyzed the morphological changes of mitochondria within tumor cells following TKI treatment. Our results indicate that mitochondrial dynamics are remodeled toward increased mitochondrial fission during the early phase of TKI treatment. Furthermore, pharmacological inhibition of mitochondrial fission further sensitizes tumor cells to EGFR-TKIs. Additionally, disrupting oxidative phosphorylation metabolism can increase the sensitivity of tumor cells to TKI treatment and reverse tumor cell resistance to TKI. Overall, these findings suggest that the metabolic reprogramming of mitochondrial OXPHOS in tumor cells mediates energy stress adaptation, altering their response to TKI treatment and providing new metabolic therapeutic targets to overcome EGFR-TKI resistance.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13470962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148726995","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}

引用次数: 0

m⁶A-Mediated Stabilization of MRPS23 Drives NSCLC Progression Via HSPA8 and ERK Signaling Modulation. m6a介导的MRPS23稳定通过HSPA8和ERK信号调节驱动NSCLC进展

IF 4.3 2区医学

Cancer Science Pub Date : 2026-08-13 DOI: 10.1111/cas.70496

Sihong Le, Yitao Le, Xianshen Sha, Feng Qiu, Ling Zhang

{"title":"m6A-Mediated Stabilization of MRPS23 Drives NSCLC Progression Via HSPA8 and ERK Signaling Modulation.","authors":"Sihong Le, Yitao Le, Xianshen Sha, Feng Qiu, Ling Zhang","doi":"10.1111/cas.70496","DOIUrl":"10.1111/cas.70496","url":null,"abstract":"Lung cancer remains the leading cause of cancer-related mortality worldwide, largely due to therapeutic resistance and tumor progression. Mitochondrial ribosomal proteins (MRPs), particularly MRPS23, have recently emerged as critical regulators of cancer progression in various malignancies, while N6-methyladenosine (m6A) modification has been established as a key epigenetic mechanism driving tumorigenesis. However, whether MRPS23 is regulated by m6A modification and contributes to lung cancer pathogenesis remains completely unexplored. Here, we identified MRPS23 as a critical oncogenic driver in non-small cell lung cancer (NSCLC). MRPS23 expression was significantly upregulated in NSCLC tissues and cell lines, and high MRPS23 levels correlated with poor patient prognosis. Mechanistically, we demonstrated that WTAP-mediated m6A methylation and subsequent IGF2BP3 recognition stabilized MRPS23 mRNA. Functionally, MRPS23 promoted lung cancer progression both in vitro and in vivo. Further mechanistic studies revealed that MRPS23 exerted its oncogenic effects through physical interaction with the molecular chaperone HSPA8, and this interaction was functionally associated with activation of the RAS-RAF-MEK-ERK signaling cascade. However, the precise molecular steps linking the MRPS23-HSPA8 complex to ERK phosphorylation remain to be fully defined. Collectively, our findings unveil a previously unrecognized m6A-dependent MRPS23/HSPA8/ERK regulatory axis in NSCLC progression, highlighting MRPS23 and its associated components as promising prognostic biomarkers and therapeutic targets.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13471123/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148727235","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}

引用次数: 0

TERT Promoter Mutations Are Preferentially Associated With the ERBB2 G776-Altered Subtype of HER2-Mutant NSCLC. TERT启动子突变优先与her2突变型NSCLC的ERBB2 g776改变亚型相关

IF 4.3 2区医学

Cancer Science Pub Date : 2026-08-13 DOI: 10.1111/cas.70504

Akihiro Yoshimura, Juichiro Yoshida, Chieko Takumi, Koichi Takayama

{"title":"TERT Promoter Mutations Are Preferentially Associated With the ERBB2 G776-Altered Subtype of HER2-Mutant NSCLC.","authors":"Akihiro Yoshimura, Juichiro Yoshida, Chieko Takumi, Koichi Takayama","doi":"10.1111/cas.70504","DOIUrl":"10.1111/cas.70504","url":null,"abstract":"HER2-mutant non-small cell lung cancer (NSCLC) comprises molecularly heterogeneous tumors with diverse ERBB2 mutation subtypes, and HER2-directed therapies have increased the need for refined molecular stratification. However, subtype-specific co-occurring genomic alterations remain incompletely characterized. We performed a two-stage clinicogenomic analysis to identify and validate recurrent co-mutations in HER2-mutant NSCLC. A public MSK-IMPACT lung adenocarcinoma cohort was used for discovery, and a nationwide Japanese real-world cohort from the Center for Cancer Genomics and Advanced Therapeutics was used for validation. In the MSK-IMPACT cohort of 2201 lung adenocarcinomas, TERT mutations were significantly enriched in ERBB2-mutant tumors compared with ERBB2-wild-type tumors (odds ratio, 2.40; 95% confidence interval, 1.12-4.70; p = 0.017). This association was reproduced in the independent validation cohort, where 16 of 174 HER2-mutant NSCLC cases harbored concurrent TERT mutations, all of which were promoter-region variants. Among the evaluated clinicogenomic variables, the ERBB2 mutation subtype was the only factor significantly associated with TERT mutation status. The ERBB2 G776-altered subtype remained independently associated with TERT mutation after multivariable adjustment (adjusted odds ratio, 7.49; 95% confidence interval, 1.81-31.0; p = 0.006). In a small exploratory subset of trastuzumab deruxtecan-treated patients (n = 52; TERT-mutated, n = 5), no statistically robust differences in treatment outcomes were observed according to TERT mutation status. TERT promoter mutations are recurrent co-mutations in HER2-mutant NSCLC and are preferentially associated with the ERBB2 G776-altered subgroup. These findings support ERBB2 subtype-aware molecular stratification and highlight previously underappreciated genomic heterogeneity within HER2-mutant NSCLC.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13470766/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148726883","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}

引用次数: 0

Quizartinib Resistance Mutations and Treatment Outcomes in Relapsed or Refractory FLT3-ITD-Positive AML. 复发或难治性flt3 - itd阳性AML的quizarinib耐药突变和治疗结果

IF 4.3 2区医学

Cancer Science Pub Date : 2026-08-12 DOI: 10.1111/cas.70485

Yuichiro Semba, Toshihiro Miyamoto, Senji Kasahara, Yoshikane Kikushige, Takahiro Maeda, Goichi Yoshimoto, Shuichi Ota, Akio Saito, Yuho Najima, Hiroki Hosoi, Daigo Niiya, Koji Kato, Koji Nagafuji, Takashi Akasaka, Tomohiko Kamimura, Atsushi Takita, Maiko Narahara, Tadashi Toki, Koichi Iwanaga, Koji Yonemoto, Mine Harada, Koichi Akashi

{"title":"Quizartinib Resistance Mutations and Treatment Outcomes in Relapsed or Refractory FLT3-ITD-Positive AML.","authors":"Yuichiro Semba, Toshihiro Miyamoto, Senji Kasahara, Yoshikane Kikushige, Takahiro Maeda, Goichi Yoshimoto, Shuichi Ota, Akio Saito, Yuho Najima, Hiroki Hosoi, Daigo Niiya, Koji Kato, Koji Nagafuji, Takashi Akasaka, Tomohiko Kamimura, Atsushi Takita, Maiko Narahara, Tadashi Toki, Koichi Iwanaga, Koji Yonemoto, Mine Harada, Koichi Akashi","doi":"10.1111/cas.70485","DOIUrl":"10.1111/cas.70485","url":null,"abstract":"Quizartinib is a FMS-like tyrosine kinase 3 (FLT3) inhibitor indicated for FLT3 internal tandem duplication (FLT3-ITD)-positive acute myeloid leukemia (AML). We aimed to evaluate quizartinib resistance mechanisms, in addition to efficacy and safety outcomes, in patients with relapsed or refractory FLT3-ITD-positive AML. This multicenter, single-arm study in Japan (jRCTs071200015) enrolled 18 patients between May 2020 and December 2022. Of these, 15 patients received oral quizartinib (up to 53 mg once daily) for up to 12 cycles of 28 days each, then were followed for 12 months. The primary endpoint was to evaluate the type and rate of quizartinib resistance mutations; secondary endpoints included composite complete remission (CRc) rate, overall response rate (ORR), hematopoietic stem cell transplantation (HSCT) rate, relapse-free survival (RFS), overall survival (OS), and adverse events (AEs). Among seven evaluable patients, acquired mutations were detected in four patients (NF1 [R2616X], CSF3R [Q754X], NRAS [G13R], and FLT3 [D835Y] in one patient each), while loss of FLT3-ITD was observed in two patients. In efficacy analyses (n = 15), CRc rate was 66.7% (95% confidence interval [CI], 38.4-88.2), ORR was 73.3% (44.9-92.2), and median OS was 13.6 months (5.4-not evaluable). Three patients (20.0%) received HSCT directly after quizartinib; in these patients, median RFS was 8.5 months (95% CI, 6.2-not evaluable). Grade ≥ 3 non-hematologic AEs and grade 1 QT prolongation were each reported in three patients (20.0%). These data offer additional information on potential resistance mechanisms in patients with relapsed or refractory FLT3-ITD-positive AML. Trial Registration: Japan Registry of Clinical Trials (jRCTs071200015).","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13464453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148714288","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}

引用次数: 0