Cancer Science最新文献

{"title":"PSMD12 Overexpression Promotes Lung Adenocarcinoma Progression via Ubiquitin–Proteasome Pathway Dysregulation","authors":"Yuya Ono,&nbsp;Hajime Otsu,&nbsp;Takaaki Masuda,&nbsp;Keisuke Kosai,&nbsp;Shohei Shibuta,&nbsp;Kosuke Hirose,&nbsp;Takashi Ofuchi,&nbsp;Yuki Ando,&nbsp;Koto Kawata,&nbsp;Yasuo Tsuda,&nbsp;Yusuke Yonemura,&nbsp;Taro Tobo,&nbsp;Tomoyoshi Takenaka,&nbsp;Tomoharu Yoshizumi,&nbsp;Koshi Mimori","doi":"10.1111/cas.70290","DOIUrl":"10.1111/cas.70290","url":null,"abstract":"<p>Lung adenocarcinoma (LUAD) is one of the most common cancers and a leading cause of cancer-related mortality worldwide, highlighting the need for novel therapeutic strategies. Proteasome 26S Subunit, Non-ATPase 12 (PSMD12), a component of the proteasomal 19S regulatory particle, is associated with tumorigenesis; however, its role in LUAD remains poorly understood. Integrative bioinformatic analysis of The Cancer Genome Atlas (TCGA) and other publicly available LUAD datasets identified <i>PSMD12</i> as a candidate driver gene on chromosome 17q, a region frequently amplified in LUAD. Clinicopathological and prognostic analyses revealed that <i>PSMD12</i> was significantly upregulated in tumor tissues because of DNA copy number gain. High <i>PSMD12</i> expression was associated with poor prognosis and advanced pathological stages. Gene set enrichment analysis of TCGA LUAD dataset demonstrated that samples with high <i>PSMD12</i> expression were enriched for cell cycle–related pathways. Using CRISPR-Cas9–mediated PSMD12 knockout and lentivirus-mediated overexpression models, we demonstrated that PSMD12 promoted tumor cell proliferation by accelerating the G2/M cell cycle transition in vitro, and xenograft experiments confirmed its tumor-promoting effect in vivo. Mechanistically, PSMD12 overexpression reduced the ubiquitination of CDK1, a key regulator of mitotic entry. Cycloheximide chase and MG132 assays confirmed that PSMD12 stabilized CDK1 by inhibiting proteasome-mediated degradation. In conclusion, we identified <i>PSMD12</i> as a novel driver gene and prognostic biomarker of LUAD. PSMD12 promoted LUAD progression by modulating CDK1 ubiquitination and enhancing cell cycle progression. These findings suggest that PSMD12 is a promising molecular target for future LUAD therapies.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"117 3","pages":"644-656"},"PeriodicalIF":4.3,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12951088/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145913518","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":"A11 Peptide Enhances Radiosensitivity by Degrading EphA2 in Nasopharyngeal Carcinoma","authors":"Ming Zhang,&nbsp;Zhi-Qiang Xiao,&nbsp;Wei Huang,&nbsp;Shan-Shan Lu,&nbsp;Hong Yi,&nbsp;Juan Feng","doi":"10.1111/cas.70291","DOIUrl":"10.1111/cas.70291","url":null,"abstract":"<p>Nasopharyngeal carcinoma (NPC) is a malignant tumor characterized by significant radioresistance and poor clinical outcomes. EphA2, a protein frequently overexpressed in various malignancies, has been implicated in promoting tumor growth and metastasis. This study explored the role and mechanism of EphA2 in driving radioresistance in NPC and evaluated the therapeutic potential of the A11 peptide in overcoming this resistance. Clinical analysis of 104 NPC tissues (26 radioresistant and 78 radiosensitive) revealed that high EphA2 expression was significantly associated with radioresistance and independently predicted reduced overall survival. Functional studies using EphA2-knockdown NPC cell lines (5-8F and CNE2) demonstrated that silencing EphA2 enhanced radiosensitivity, as evidenced by in vitro assays including clonogenic formation, apoptosis analysis, and γ-H2AX detection, as well as in vivo xenograft experiments. Mechanistically, EphA2 drives radioresistance through a radiation-induced RSK-EphA2-AKT signaling cascade. Specifically, radiation triggered RSK-mediated phosphorylation of EphA2 at Ser897, which subsequently facilitated AKT phosphorylation at Ser473. The A11 peptide broke this signaling cascade by degrading EphA2 and blocking its S897 phosphorylation, thereby markedly enhancing radiosensitivity. These findings indicate that EphA2 overexpression and its S897 phosphorylation play a critical role in NPC radioresistance. The A11 peptide emerges as a promising therapeutic agent by degrading EphA2 and blocking its phosphorylation, offering a potential strategy to enhance radiotherapy efficacy and improve outcomes in NPC patients.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"117 3","pages":"657-669"},"PeriodicalIF":4.3,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12951089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145745347","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":"KAT2A Deficiency Suppresses Lung Cancer Progression by Downregulating MYC Through Decreasing MYC Succinylation","authors":"Junping Li,&nbsp;Feng Zhao,&nbsp;Zhongchao Wang,&nbsp;Shaojun Yang,&nbsp;Zhichao Lu,&nbsp;Xiaoyan Li,&nbsp;Jincheng Song,&nbsp;Zhaoxia Dai","doi":"10.1111/cas.70286","DOIUrl":"10.1111/cas.70286","url":null,"abstract":"<p>Succinylation has been shown to promote lung cancer development, but its mechanism remains incompletely understood. KAT2A, a succinyltransferase, acts as an oncogene in multiple cancers, but its role in mediating lung cancer progression is unclear. This study aimed to investigate the mechanism by which KAT2A regulates lung cancer progression via succinylation. KAT2A expression was analyzed using UALCAN, GEPIA, and Kaplan–Meier Plotter databases, and validated in lung cancer cell lines and patient-derived tissues. Quantitative real-time PCR, Cell Counting Kit-8 (CCK-8), EdU staining, and flow cytometry were performed to assess KAT2A's role in lung cancer cell proliferation and apoptosis. KAT2A's target proteins were predicted using LinkedOmics and STRING databases. Additionally, in vivo xenograft models were established to evaluate the effect of KAT2A knockdown on tumor growth. Results indicated that KAT2A expression was significantly elevated in lung cancer cells and tissues and was associated with poor prognosis. KAT2A knockdown inhibited proliferation and promoted apoptosis in lung cancer cells, whereas MYC overexpression reversed these effects. Mechanistically, KAT2A knockdown downregulated MYC by reducing succinylation at K370 and K386 residues. Mutation of these sites abrogated the proliferative effect of MYC overexpression and restored apoptotic activity. Furthermore, in vivo experiments demonstrated that KAT2A knockdown inhibited tumor growth and reduced MYC succinylation. Our findings demonstrate that KAT2A functions as an oncogene in lung cancer by enhancing MYC succinylation. This study identifies KAT2A as a promising therapeutic target for lung cancer.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"117 3","pages":"631-643"},"PeriodicalIF":4.3,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12951091/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145709152","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":"Urinary Tumor DNA to Identify Candidates for Repeat Transurethral Resection in Non-Muscle-Invasive Bladder Cancer","authors":"Zihan Xue,&nbsp;Yunkai Qie,&nbsp;Chong Shen,&nbsp;Zhouliang Wu,&nbsp;Houyuan Chen,&nbsp;Yuda Lin,&nbsp;Rongjiang Li,&nbsp;Shiwang Huang,&nbsp;Hailong Hu","doi":"10.1111/cas.70311","DOIUrl":"10.1111/cas.70311","url":null,"abstract":"<p>Repeat transurethral resection of bladder tumor (re-TURBT) is commonly recommended for patients with non–muscle-invasive bladder cancer (NMIBC) with high-risk features, although many individuals may undergo unnecessary procedures that increase morbidity without clear benefit. Urinary tumor DNA (utDNA) has emerged as a promising biomarker, and we evaluated the performance of a multidimensional utDNA assay (utLIFE) in this context. In a retrospective cohort of 161 patients who underwent re-TURBT between May 2020 and May 2025, urine samples collected 2–6 weeks after initial TURBT were analyzed using utLIFE, which integrates shallow whole-genome sequencing and targeted sequencing of 155 genes with machine learning–based classification. Residual tumor was identified in 35% of patients, and utLIFE demonstrated high diagnostic accuracy, with sensitivity of 80.7%, specificity of 96.2%, and overall accuracy of 90.7%, markedly outperforming urine cytology. A positive utLIFE result was the strongest independent predictor of residual disease (OR = 77.5, 95% CI: 22.4–268.2, <i>p</i> &lt; 0.001). During a median follow-up of 32.5 months, recurrence occurred in 20.5% of patients; recurrence was defined as urothelial tumor relapse within the urinary tract and did not include distant metastasis. utLIFE positivity was significantly associated with shorter recurrence-free survival (HR = 16.4, 95% CI: 2.7–101.8, <i>p</i> = 0.003). Longitudinal testing further revealed that utDNA positivity frequently preceded cystoscopic evidence of recurrence by several months. These findings highlight the strong diagnostic and prognostic value of utDNA in identifying residual disease and predicting recurrence, supporting its potential role in refining postoperative management strategies for NMIBC.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"117 3","pages":"787-796"},"PeriodicalIF":4.3,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12951098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145828811","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":"Longitudinal Impact of Urinary Diversion on Health-Related Quality of Life After Radical Cystectomy: A Multicenter Study in Japan","authors":"Shuhei Yamada,&nbsp;Miho Sato,&nbsp;Takahiro Osawa,&nbsp;Toru Harabayashi,&nbsp;Jun Miki,&nbsp;Takashi Kobayashi,&nbsp;Katsuyoshi Hashine,&nbsp;Atsunari Kawashima,&nbsp;Takashi Matsumoto,&nbsp;Takanori Mochizuki,&nbsp;Rikiya Taoka,&nbsp;Fumihiko Urabe,&nbsp;Shuichi Tatarano,&nbsp;Atsuro Sawada,&nbsp;Takahiro Kojima,&nbsp;Atsushi Takahashi,&nbsp;Akira Yokomizo,&nbsp;Shigetaka Suekane,&nbsp;Kohei Hashimoto,&nbsp;Yasuhiro Hashimoto,&nbsp;Junji Yatsuda,&nbsp;Ken Morita,&nbsp;Keita Kobayashi,&nbsp;Yohei Satake,&nbsp;Ataru Sazawa,&nbsp;Yoshiyuki Matsui,&nbsp;Yoichi M. Ito,&nbsp;Sayaka Shimizu,&nbsp;Shunichi Fukuhara,&nbsp;Hiroyuki Nishiyama,&nbsp;Hiroshi Kitamura,&nbsp;Nobuo Shinohara,&nbsp;the Japanese Urological Oncology Group","doi":"10.1111/cas.70289","DOIUrl":"10.1111/cas.70289","url":null,"abstract":"<p>This multicenter longitudinal study was conducted across 24 institutions in Japan to examine the impact of urinary diversion on health-related quality of life (HRQOL) among bladder cancer patients who underwent radical cystectomy (RC). We evaluated bladder cancer-specific HRQOL and general HRQOL via the bladder cancer index (BCI) and the QOL General (QGEN-8), respectively, before the operation and at 3, 6, and 12 months postoperatively. The scores were compared across urinary diversion groups as well as across different time points within each urinary diversion group with linear mixed-effects models. Data from 227 patients were analyzed (151 with ileal conduits, 45 with ureterostomy, and 31 with neobladders). Neobladder patients were more likely to experience longitudinal impacts of their urinary diversion on urinary function than ileal conduit or ureterostomy patients were. Compared with that at baseline, the bowel function of neobladder patients remained impaired 12 months after surgery. All urinary diversion groups had worse sexual function scores at 3 and 6 months than at baseline, and the ileal conduit and neobladder groups had significantly worse sexual function scores at 12 months than at baseline. On the other hand, there was no significant difference in bother scores in the urinary, bowel, or sexual domain. The generic HRQOL was maintained from the preoperative to the postoperative period in all urinary diversion groups. This study explored longitudinal changes in HRQOL after RC, and the findings may help inform patient counseling regarding possible QOL trajectories.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"117 3","pages":"739-748"},"PeriodicalIF":4.3,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12951116/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145901560","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":"Atezolizumab + Chemotherapy for Advanced Non-Small Cell Lung Cancer in Japanese Clinical Practice (J-TAIL-2)","authors":"Hiroshige Yoshioka,&nbsp;Makoto Nishio,&nbsp;Kadoaki Ohashi,&nbsp;Atsushi Osoegawa,&nbsp;Eiki Kikuchi,&nbsp;Hideharu Kimura,&nbsp;Yasushi Goto,&nbsp;Junichi Shimizu,&nbsp;Eisaku Miyauchi,&nbsp;Ichiro Yoshino,&nbsp;Toshihiro Misumi,&nbsp;Yasutaka Watanabe,&nbsp;Akito Hata,&nbsp;Akira Kisohara,&nbsp;Shoichi Kuyama,&nbsp;Masafumi Yamaguchi,&nbsp;Asako Miwa,&nbsp;Shunichiro Iwasawa,&nbsp;Misa Tanaka,&nbsp;Akihiko Gemma","doi":"10.1111/cas.70242","DOIUrl":"10.1111/cas.70242","url":null,"abstract":"<p>First-line atezolizumab combination therapies were approved for the treatment of metastatic non-small cell lung cancer (NSCLC) based on results from the global phase 3 trials IMpower130, IMpower132, and IMpower150. These trials reported 12-month overall survival (OS) rates of 60%–67% with atezolizumab combination therapy. J-TAIL-2 (NCT04501497), a prospective, multicenter, observational study, evaluated atezolizumab combination therapy in routine clinical practice in Japan. Patients ≥ 20 years old with NSCLC received atezolizumab plus carboplatin and nab-paclitaxel (atezo + CnP), atezolizumab plus carboplatin or cisplatin plus pemetrexed (atezo + PP), or atezolizumab plus bevacizumab plus carboplatin and paclitaxel (atezo + bev + CP) in clinical practice. The primary endpoint was the 12-month OS rate. Secondary endpoints included OS, progression-free survival, and subgroup analyses, including IMpower-unlike (did not meet the main eligibility criteria of each IMpower trial) and IMpower-like patients. In total, 814 patients were enrolled (atezo + CnP, <i>n</i> = 217; atezo + PP, <i>n</i> = 211; atezo + bev + CP, <i>n</i> = 386). The IMpower-unlike group included patients with Eastern Cooperative Oncology Group performance status ≥ 2, autoimmune disease, or interstitial lung disease. Twelve-month OS rates (95% confidence interval [CI]) were 62.9% (55.8–69.2), 72.1% (65.2–77.9), and 68.3% (63.2–72.9) with atezo + CnP, atezo + PP, and atezo + bev + CP, respectively. OS hazard ratios (95% CI) in the IMpower-unlike vs. -like subgroups were 1.36 (0.91–2.05), 1.08 (0.70–1.68), and 1.49 (1.09–2.06), respectively. No new safety signals were observed. Real-world efficacy and safety for each atezolizumab combination were comparable to those in the relevant IMpower trials.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"117 3","pages":"727-738"},"PeriodicalIF":4.3,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12951125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145726745","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":"Targeting SPP1-CD44-Hedgehog Axis Elicits Therapeutic Effects in Hepatocellular Carcinoma by Suppressing Intratumoral Fibrosis","authors":"Atsushi Nara,&nbsp;Shu Shimada,&nbsp;Yoshimitsu Akiyama,&nbsp;Megumi Hatano,&nbsp;Yusuke Chino,&nbsp;Suguru Miyazawa,&nbsp;Hanako Tamura,&nbsp;Daisuke Asano,&nbsp;Yoshiya Ishikawa,&nbsp;Hiroki Ueda,&nbsp;Shuichi Watanabe,&nbsp;Eriko Katsuta,&nbsp;Keiichi Akahoshi,&nbsp;Kenichi Ohashi,&nbsp;Minoru Tanabe,&nbsp;Daisuke Ban,&nbsp;Shinji Tanaka","doi":"10.1111/cas.70296","DOIUrl":"10.1111/cas.70296","url":null,"abstract":"<p>Advanced hepatic fibrosis is a major risk factor for cirrhosis and hepatocellular carcinoma (HCC), and it is required to identify a key mediator involved in intratumoral fibrosis and HCC development. Transcriptomic analysis of 372 HCC samples using publicly available datasets revealed that <i>SPP1</i> was significantly upregulated in fibrotic HCC tissues and associated with unfavorable outcomes. Immunohistochemical analysis of 103 HCC tissues and single-cell RNA sequencing (scRNA-seq) analysis of 228,564 live cells identified <i>SPP1</i> overexpression in HCC cells, which strongly correlated with intratumoral fibrosis. In xenograft models, HCC cells with SPP1 overexpression (SPP1-OE) exhibited enhanced fibrosis and tumor growth. Coculture assay demonstrated that SPP1-OE cells stimulated hepatic stellate cells (HSCs), and gene set enrichment analysis and differential gene expression analysis elucidated the activation of the Hedgehog signaling pathway and upregulation of <i>GLI1</i> in HSCs. Cell–cell interaction prediction analysis using scRNA-seq data suggested that SPP1-CD44 signaling transduction might contribute to HSC activation. Pharmacological inhibition of GLI1 with the SMO inhibitor vismodegib suppressed HSC activation in vitro and reduced fibrosis and tumor growth in vivo. These findings indicate that SPP1 promotes intratumoral fibrosis and HCC progression through the SPP1-CD44-GLI1 axis, highlighting its potential as a prognostic biomarker and therapeutic target. Inhibition of SPP1-CD44-Hedgehog signaling may provide a promising strategy to mitigate fibrosis and improve HCC patient outcomes.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"117 3","pages":"670-682"},"PeriodicalIF":4.3,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12951113/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145850859","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":"Impact of Achieving Progression-Free Survival 24 on Subsequent Overall Survival in Diffuse Large B-Cell Lymphoma Patients","authors":"Ayumi Fujimoto,&nbsp;Wataru Munakata,&nbsp;Gakuto Ogawa,&nbsp;Ryunosuke Machida,&nbsp;Tomotaka Suzuki,&nbsp;Kazuyuki Shimada,&nbsp;Tsutomu Kobayashi,&nbsp;Ken Ohmachi,&nbsp;Tomohiro Kinoshita,&nbsp;Kiyoshi Ando,&nbsp;Dai Maruyama,&nbsp;Hirokazu Nagai","doi":"10.1111/cas.70304","DOIUrl":"10.1111/cas.70304","url":null,"abstract":"<p>The impact of achieving progression-free survival at 24 months (PFS24) on subsequent survival in patients with diffuse large B-cell lymphoma (DLBCL) relative to the general population remains debatable. We assessed the impact of achieving PFS24 in newly diagnosed DLBCL patients using data from JCOG0601, a prospective study of DLBCL patients treated with R-CHOP. Among 409 eligible patients (median follow-up: 5.3 years), 334 (82%) achieved PFS24, whereas 66 (16%) did not. Patients who achieved PFS24 had significantly better overall survival (OS) than those who did not (median OS, not reached vs. 1.3 years; <i>p</i> &lt; 0.001). Similar results were observed for PFS12 and PFS60. The OS for patients after achieving PFS24 or PFS60 was not markedly different from that of the age-, sex-, and calendar period-matched Japanese general population (PFS24: standardized mortality ratio [SMR] 1.29, 95% confidence interval [CI] 0.72–2.12, <i>p</i> = 0.39; PFS60: SMR 1.43, 95% CI 0.47–3.33, <i>p</i> = 0.55). Conversely, the OS for patients after achieving PFS12 was significantly worse than that of the general population (SMR 2.30, 95% CI 1.59–3.22, <i>p</i> &lt; 0.001). The primary cause of death among patients who achieved PFS12 was DLBCL, whereas the mortality rate from DLBCL among those who achieved PFS24 or PFS60 was less than 5%. Multivariable analysis showed that having two or more extranodal involvements (OR 2.76 [95% CI 1.39–5.46], <i>p</i> = 0.004) was the only significant risk factor for failing to achieve PFS24. Our findings suggest that PFS24 can serve as an early endpoint of OS in patients with DLBCL.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"117 3","pages":"769-776"},"PeriodicalIF":4.3,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12951095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145795262","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":"IMpower010: 5-Year Outcomes of Atezolizumab in Japanese Patients With Resected Stage IB–IIIA Non-Small Cell Lung Cancer","authors":"Morihito Okada,&nbsp;Shunichi Sugawara,&nbsp;Yasutaka Watanabe,&nbsp;Haruhiro Saito,&nbsp;Toyofumi F. Chen-Yoshikawa,&nbsp;Yasushi Goto,&nbsp;Wataru Nishio,&nbsp;Shizuka Nakagawa,&nbsp;Morihiko Hayashi,&nbsp;Hirotsugu Kenmotsu","doi":"10.1111/cas.70297","DOIUrl":"10.1111/cas.70297","url":null,"abstract":"<p>The global Phase 3 IMpower010 study (NCT02486718) evaluated atezolizumab versus best supportive care (BSC) after complete resection and adjuvant platinum-based chemotherapy in patients with stage IB–IIIA non-small cell lung cancer (NSCLC). We report updated efficacy and safety results from the disease-free survival (DFS) final and overall survival (OS) second interim analyses, with ≥ 5 years of follow-up in Japanese patients. Patients who received 1–4 21-day chemotherapy cycles after surgery were randomized 1:1 to receive atezolizumab 1200 mg every 3 weeks (≤ 16 cycles) or BSC. Of 149 patients enrolled, 117 were randomized to the intention-to-treat (ITT) population (atezolizumab <i>n</i> = 59; BSC <i>n</i> = 58). At data cutoff (January 26, 2024), unstratified hazard ratios (HRs) (95% confidence interval [CI]) for DFS in the atezolizumab versus BSC arms were 0.54 (0.28–1.07) in the stage II–IIIA programmed death-ligand 1 (PD-L1) tumor cell (TC) ≥ 1% (<i>n</i> = 74), 0.64 (0.27–1.52) in the stage II–IIIA PD-L1 TC 1%–49% (<i>n</i> = 34), 0.52 (0.17–1.54) in the stage II–IIIA PD-L1 TC ≥ 50% (<i>n</i> = 40), 0.58 (0.34–1.00) in the stage II–IIIA all-randomized (<i>n</i> = 113), and 0.57 (0.34–0.98) in the ITT populations. OS remained immature; median OS was not reached in both treatment arms for all subgroups. Grade 3/4 adverse events occurred in 15 (26.8%) and 7 patients (12.1%) in the atezolizumab and BSC arms, respectively; no deaths were reported. In this exploratory subgroup analysis, adjuvant atezolizumab demonstrated numerically improved DFS and OS versus BSC in Japanese patients and was well tolerated, similar to the global IMpower010 population.</p><p><b>Trial Registration:</b> ClinicalTrials.gov identifier: NCT02486718</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"117 3","pages":"749-758"},"PeriodicalIF":4.3,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12951087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145795228","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":"Phase 1/2 Study of Crizotinib in Children With Relapsed/Refractory ALK-Positive Anaplastic Large Cell Lymphoma or Neuroblastoma in Japan","authors":"Tetsuya Mori,&nbsp;Akiko Kada,&nbsp;Tomoo Osumi,&nbsp;Daisuke Tomizawa,&nbsp;Yuhki Koga,&nbsp;Reiji Fukano,&nbsp;Kengo Takeuchi,&nbsp;Ukihide Tateishi,&nbsp;Osamu Miyazaki,&nbsp;Ryuta Asada,&nbsp;Akiko M. Saito,&nbsp;Kei Fukuhara,&nbsp;Masahiro Sekimizu","doi":"10.1111/cas.70308","DOIUrl":"10.1111/cas.70308","url":null,"abstract":"<p>Clinical development of crizotinib in children with ALK-positive anaplastic large cell lymphoma (ALCL) was advanced in the US but not in Japan. The objectives of phase 1 part of a clinical study in Japan were to assess the safety and pharmacokinetics and determine the recommended phase 2 dose (RP2D) of crizotinib in children with relapsed/refractory (R/R) ALK-positive ALCL or neuroblastoma (NB). Two dose levels (165 and 280 mg/m² twice daily (BID)) were planned to be evaluated. The aim of phase 2 part of the study was to assess the antitumor activity of crizotinib at the RP2D in children with R/R ALK-positive ALCL. Seven patients were eligible for phase 1 part, 5 with ALCL and 2 with NB. All 7 patients received crizotinib at a starting dose of 165 mg/m² BID, with 1 dose-limiting toxicity observed (grade 3 gamma-glutamyltransferase increased). The most common grade 3 or 4 adverse event was neutropenia (71%). The steady-state <i>C</i>_max and AUC_tau of crizotinib at 165 mg/m² BID were higher than expected. Considering the risk of a greater incidence of severe neutropenia, we decided that the 165 mg/m² BID be the RP2D without evaluation at 280 mg/m² BID. A total of 11 patients with ALK-positive ALCL were enrolled in the phase 2 part. The objective response rate was 72.7% (90% CI, 43.6%–92.1%). One patient permanently discontinued crizotinib due to disease progression. Crizotinib at 165 mg/m² BID was well tolerated and showed favorable antitumor activity in children with R/R ALK-positive ALCL.</p><p><b>Trial Registration:</b> UMIN-CTR: UMIN000028075</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"117 3","pages":"777-786"},"PeriodicalIF":4.3,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12951090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145850677","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}