Cancer reports最新文献

{"title":"Safety and Effectiveness of Denileukin Diftitox-cxdl in Patients With Relapsed/Refractory Peripheral T-Cell Lymphoma and Cutaneous T-Cell Lymphoma: An All-Case Post-Marketing Study in Japan","authors":"Tatsuro Jo,&nbsp;Kota Matsumoto,&nbsp;Mika Ishii,&nbsp;Koji Izutsu","doi":"10.1002/cnr2.70641","DOIUrl":"10.1002/cnr2.70641","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Denileukin diftitox (DD)-cxdl, a fusion protein comprising diphtheria toxin fragments and human interleukin-2, is a treatment for peripheral T-cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL). Previous trials have enrolled a limited number of patients, and there is a need to evaluate DD-cxdl in a more diverse population, including those with different ages and treatment histories.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This observational post-marketing study (19 May 2021 to 1 February 2024) was conducted in over 200 institutions in Japan to evaluate the safety and effectiveness of DD-cxdl in patients with relapsed or refractory PTCL and CTCL (NCT05137847; jRCT2031220196). Patient characteristics, status of drug administration, adverse events (AEs), adverse drug reactions (ADRs), and effectiveness were assessed. Capillary leak syndrome was specified as an AE of special interest.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Data from 104 patients were analyzed (PTCL: 85; CTCL: 19), including 57 male patients (54.8%). The median age was 74 (range: 20–88) years. The median number of prior chemotherapy lines was 3.5 (1.0–10.0), and approximately half (55.8%) of the patients discontinued treatment during cycle 1. Most patients experienced AEs (94.2%) and ADRs (84.6%), and the most common serious ADR was capillary leak syndrome (22.1%). Effectiveness could be assessed in 80/104 patients. The overall objective response rate was 16.3% (95% confidence interval: 8.9, 26.2), and in patients with PTCL and CTCL it was 15.4% (7.6, 26.5) and 20.0% (4.3, 48.1), respectively. Four patients (6.2%) with PTCL achieved a complete response.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This is the first observational study to evaluate the safety and effectiveness of DD-cxdl in Japanese patients with relapsed or refractory PTCL and CTCL in daily clinical practice. No new safety concerns were identified. Clinicians should remain aware of the risk of capillary leak syndrome.</p>\u0000 \u0000 <p><b>Trail Registration:</b> ClinicalTrials.gov identifier: NCT05137847 and Japan Registry of Clinical Trials identifier: jRCT2031220196.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"9 8","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cnr2.70641","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148759146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of Nivolumab in Chemotherapy-Resistant Mesothelioma of the Tunica Vaginalis Testis: A Case Report","authors":"Haruki Koyanagi,&nbsp;Takashi Kawahara,&nbsp;Natsuki Inagawa,&nbsp;Miho Shiga,&nbsp;Hiromichi Sakurai,&nbsp;Akane Yamaguchi,&nbsp;Kouzaburou Tanuma,&nbsp;Satoshi Nitta,&nbsp;Kosuke Kojo,&nbsp;Masanobu Shiga,&nbsp;Yoshiyuki Nagumo,&nbsp;Atsushi Ikeda,&nbsp;Shuya Kandori,&nbsp;Akio Hoshi,&nbsp;Hiromitsu Negoro,&nbsp;Hitomi Kawai,&nbsp;Daisuke Matsubara,&nbsp;Hiroyuki Nishiyama","doi":"10.1002/cnr2.70647","DOIUrl":"https://doi.org/10.1002/cnr2.70647","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Mesothelioma of the tunica vaginalis testis is a rare neoplasm, accounting for less than 1% of all mesothelioma cases. Due to the rarity of this disease, a standard treatment has not been established. Clinical management is generally adapted from the strategies used for pleural mesothelioma. Although immune checkpoint inhibitors (ICIs) have demonstrated efficacy in treating pleural mesothelioma, their role in mesothelioma of the tunica vaginalis testis remains uncharacterized due to a lack of evidence. This is the first report documenting a clinical response to nivolumab in chemoresistant mesothelioma of the tunica vaginalis testis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Case</h3>\u0000 \u0000 <p>A 71-year-old man presented with painless left scrotal swelling and was initially diagnosed with a hydrocele at the referring hospital. One year later, hydrocelectomy revealed partial thickening of the tunica without malignancy. A subsequent magnetic resonance imaging analysis revealed a new intratesticular nodule. Orchiectomy was performed, and the pathological findings revealed an epithelioid mesothelioma. He was referred to Tsukuba University Hospital for further treatment. He also had a history of Self-Defense Force service, which suggested possible asbestos exposure. Imaging revealed pelvic lymphadenopathy with fluorodeoxyglucose uptake in the right external iliac lymph nodes. He received four cycles of cisplatin and pemetrexed every 3 weeks, resulting in stable disease. Bilateral pelvic lymph node dissection was performed and confirmed the presence of metastatic mesothelioma. Nine months after the surgery, bilateral inguinal lymph node recurrence occurred, and he received cisplatin monotherapy because of renal impairment. Despite four additional cycles of cisplatin monotherapy, the disease progressed. Therefore, chemotherapy was discontinued, and nivolumab was administered. Nivolumab resulted in sustained tumor shrinkage. However, after 3 months of treatment, he developed immune-related encephalitis requiring corticosteroid therapy and nivolumab discontinuation. After 16 months of nivolumab initiation, he was dead from the disease.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This is the first report documenting the clinical response of a chemoresistant mesothelioma of the tunica vaginalis testis to nivolumab. ICIs are a promising treatment option for this rare and challenging disease.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"9 8","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cnr2.70647","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148753689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic and Predicted Significance of PKLR in Patients With Cholangiocarcinoma","authors":"Biyan Gong,&nbsp;Xuejun Xu,&nbsp;Tubing Xu,&nbsp;Dong Zhang,&nbsp;Li Yang,&nbsp;Cailing Li,&nbsp;Tingjun Li,&nbsp;Yuandeng Luo","doi":"10.1002/cnr2.70649","DOIUrl":"https://doi.org/10.1002/cnr2.70649","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cholangiocarcinoma (CCA) is a highly heterogeneous malignancy with a poor prognosis. However, the molecular mechanisms underlying CCA and its treatment options remain unclear and limited.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This study aims to identify novel prognostic biomarkers and potential therapeutic targets for CCA through transcriptomics and whole-exome sequencing analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>We analyzed the relationship between overall survival and various risk factors in 255 CCA samples from a published dataset and 36 samples from The Cancer Genome Atlas (TCGA) database. Transcriptomics analysis was used to identify genes whose expression plays a crucial role in CCA development and progression. Targeted drug databases were used to examine which gene expression signatures represent potential therapeutic targets for CCA. Mutated genes were analyzed to explore potential mechanisms. Standard statistical methods were applied to analyze associations between clinical data and candidate targets. A nomogram was constructed to predict the prognostic impact of the optimal candidate. Cell experiments were used to demonstrate the role of PKLR in CCA growth and metastasis. We identified FOLH1, PKLR, PTH1R, GPR114, KCNH2, LCN2, MMP10, PORCN, RIPK3, and SRPK3 as potential therapeutic targets for CCA, with PKLR being the most promising candidate based on the computational analyses. PKLR was lowly expressed in CCA tissues. PKLR expression was closely associated with ARID1A and KRAS mutations. PKLR mRNA levels were significantly correlated with tumor size (<i>p</i> = 0.024) and metastasis (<i>p</i> = 0.014). Low PKLR expression in CCA was positively associated with poor survival. A nomogram accurately predicted the prognosis of CCA patients based on PKLR expression levels. Silencing PKLR expression promotes growth and metastasis of CCA in vitro.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings indicate that PKLR, an independent protective factor in CCA, is a potential prognostic biomarker and a candidate for further investigation as a therapeutic target. PKLR expression is significantly associated with ARID1A and KRAS mutations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"9 8","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cnr2.70649","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148753690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic, Trop-2, and Immune Profiles of Carcinomatous and Sarcomatous Components in Ovarian Carcinosarcoma","authors":"Tomomi Sakamaki,&nbsp;Tatsuyuki Chiyoda,&nbsp;Kohei Nakamura,&nbsp;Reika Takamatsu,&nbsp;Ryutaro Kawano,&nbsp;Daisuke Ochiai,&nbsp;Mitsuyo Jisaka,&nbsp;Mio Takahashi,&nbsp;Takuma Yoshimura,&nbsp;Yumiko Kimura,&nbsp;Shinya Oki,&nbsp;Kensuke Sakai,&nbsp;Tomoko Yoshihama,&nbsp;Hiroshi Nishihara,&nbsp;Wataru Yamagami","doi":"10.1002/cnr2.70659","DOIUrl":"https://doi.org/10.1002/cnr2.70659","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Ovarian carcinosarcoma (OCS) is a rare, aggressive tumor composed of both carcinomatous and sarcomatous components, typically associated with poor prognosis. Due to its rarity, the molecular characteristics, immune microenvironment, and optimal treatment of OCS remain unclear. This study aimed to characterize the genomic profiles, Trop-2 expression, and immune microenvironment of the carcinomatous and sarcomatous components of OCS separately, and to explore candidate therapeutic targets for this rare and aggressive tumor.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Case</h3>\u0000 \u0000 <p>This retrospective, single-institution study analyzed nine cases of ovarian or fallopian tube carcinosarcoma treated between 2013 and 2023. Targeted next-generation sequencing of 160 cancer-related genes was performed in eight cases, and immunohistochemistry for p53, Trop-2, CD8, and PD-L1 was performed in nine cases, with the carcinomatous and sarcomatous components evaluated separately whenever they were separable. All tumors contained high-grade serous carcinoma components. Targeted sequencing revealed <i>TP53</i> mutations in all samples. Most genetic alterations were shared by both components, supporting the role of epithelial-mesenchymal transition in OCS pathogenesis. Amplifications in <i>CCND1</i>, <i>CCNE1</i>, <i>PRKCI</i>, and <i>GNAS</i> (37.5%), and <i>ERBB2</i> (12.5%) were detected, and whole genome duplication was observed in two cases (25%). One case (12.5%) showed high microsatellite instability and was associated with Lynch syndrome. Immunohistochemistry showed Trop-2 positivity in all carcinomatous components, with a trend toward higher expression compared with sarcomatous areas (<i>p</i> = 0.0625). CD8 and PD-L1 levels were low, consistent with a relatively non-inflamed, immune-cold-like microenvironment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings suggest molecular similarities between OCS and high-grade serous carcinoma and highlight the role of epithelial-mesenchymal transition. The low immune marker expression suggests limited benefit from immune checkpoint inhibitors, except in select Lynch syndrome cases. In contrast, the consistently high Trop-2 expression in the carcinomatous component may warrant further investigation of Trop-2-targeted antibody–drug conjugates as a hypothesis-generating therapeutic candidate for OCS.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"9 8","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cnr2.70659","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148753695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TP53 Mutation and Tumor-Infiltrating Lymphocytes as Predictors of PD-1/PD-L1 Inhibitor Efficacy in PD-L1-High Advanced NSCLC","authors":"Hui Yan,&nbsp;Qian Xu,&nbsp;Yushuang Zheng,&nbsp;Meng Shen,&nbsp;Dapeng Li","doi":"10.1002/cnr2.70648","DOIUrl":"https://doi.org/10.1002/cnr2.70648","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Programmed death-ligand 1 (PD-L1) expression is widely used to guide immune checkpoint inhibitor (ICI) therapy in advanced nonsmall cell lung cancer (NSCLC); however, substantial heterogeneity in clinical outcomes persists among patients with high PD-L1 expression. Reliable biomarkers for further stratifying this population are still lacking. This study investigated whether genomic alterations and features of the tumor immune microenvironment could explain this variability.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We conducted a retrospective single-center study including 91 patients with advanced NSCLC and PD-L1 tumor proportion score (TPS) ≥ 50% who received ICI-based therapy. Clinical outcomes were assessed according to PD-L1 expression levels, genomic profiles, and tumor immune microenvironment characteristics. Tumor-infiltrating lymphocytes (TILs) and tertiary lymphoid structures (TLSs) were evaluated in available tumor specimens from 75 patients. Multiplex immunohistochemistry (mIHC) was performed in a subset of 30 patients to characterize the immune cellular composition underlying TIL-based stratification. Kaplan–Meier survival analysis and multivariable Cox regression were used to identify factors associated with progression-free survival (PFS) and overall survival (OS).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;At a median follow-up of 19.1 months, the objective response rate was 31.9%, the median PFS was 10.7 months, and the median OS was 43.5 months. No significant survival differences were observed between the TPS 50%–89% and TPS ≥ 90% subgroups. TP53 mutation was associated with shorter PFS and remained an independent adverse prognostic factor. In contrast, high TIL infiltration was independently associated with improved PFS and OS, and this OS benefit was most pronounced in the TPS ≥ 90% subgroup. mIHC analysis revealed that high-TIL tumors exhibited increased stromal CD8&lt;sup&gt;+&lt;/sup&gt; T-cell infiltration, enriched NK-cell populations, and a more proinflammatory macrophage profile, providing biological support for TIL-based stratification. TLS presence was not significantly associated with survival outcomes.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusions&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;PD-L1 expression alone does not fully account for the outcome heterogeneity observed in PD-L1-high NSCLC treated with ICIs. Integrating genomic alterations—particularly TP53 mutation status—with tumor immune microenvironment features, such as TIL density, may help refine prognostic stratification in this population.&lt;/p&gt;\u0000 ","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"9 8","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cnr2.70648","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148753644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment, Monitoring, and Management of Patients With Relapsed/Refractory Chronic Lymphocytic Leukemia and Mantle Cell Lymphoma: Evidence From a Multi-Country Needs Assessment","authors":"Patrice Lazure,&nbsp;Toby A. Eyre,&nbsp;Carsten Utoft Niemann,&nbsp;Nirav N. Shah,&nbsp;Martin Dreyling,&nbsp;Florence Cymbalista,&nbsp;Sophie Peloquin,&nbsp;Serge Znamensky,&nbsp;Benjamin Goebel,&nbsp;Suzanne Murray","doi":"10.1002/cnr2.70655","DOIUrl":"https://doi.org/10.1002/cnr2.70655","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The treatment landscape for relapse/refractory chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) has evolved with recent novel agents. With the availability of novel agents that slow disease progression, managing treatment side effects and monitoring response in patients with these hematologic malignancies may present a challenge for healthcare providers. The imperative to engage patients in the management of their condition demands that specialists are knowledgeable about new treatment options and are skilled and confident in educating patients to manage and monitor for potential side effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This study aimed to establish the current knowledge, skills and confidence levels of oncologists, hematologists and hematologist-oncologists (ONC/HEM) and identify the challenges they experience when managing and monitoring treatment and engaging patients with CLL or MCL in shared decision-making. The long-term aim is to inform evidence-based continuing medical education to optimize ONC/HEM competencies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>This cross-sectional study employed a quantitative survey, completed by 285 ONC/HEM practicing in academic or community settings in Brazil, France, Germany, the United Kingdom, and the United States. Using 5-point Likert-type scales, participants reported their knowledge/skills/confidence levels, and their agreement with selected statements. Sub-optimal levels of knowledge/skills to identify and manage side effects associated with treatments for CLL or MCL were reported. Challenges with patient risk stratification and engaging patients in shared decision-making were reported, with a greater proportion reported by those in community settings. Of note, 31% of participants reported sub-optimal skills identifying patients at higher risk for progression and using stratification to plan and manage treatment, and 58% never/rarely/sometimes considered patients' concerns about treatment safety.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Continuing medical education activities to improve knowledge of new treatments and associated pathways for patients with CLL or MCL, and to develop skills/confidence to engage in shared decision-making are recommended. Setting-specific issues should be integrated into interventions to ensure relevant educational support for the ONC/HEM.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"9 8","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cnr2.70655","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148753893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association Between Metformin Use and Risk of Lung Cancer in Patients With Type 2 Diabetes: A Systematic Review and Meta-Analysis","authors":"Mehdi Karimi,&nbsp;Farnaz Hooshmand,&nbsp;Kiana Mohammadian,&nbsp;Seyed Morteza Ali Pourfaraji,&nbsp;Masoud Mortezazadeh","doi":"10.1002/cnr2.70651","DOIUrl":"10.1002/cnr2.70651","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aim</h3>\u0000 \u0000 <p>Lung cancer remains one of the leading causes of cancer-related mortality worldwide. Type 2 diabetes mellitus (T2DM), the most prevalent endocrine disorder, is commonly managed with Metformin, an antidiabetic medication that has demonstrated potential anticancer properties. This meta-analysis aimed to discover the association between Metformin use and the risk of lung cancer in patients with T2DM.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A comprehensive search of online databases was conducted up to January 1, 2026, to identify relevant observational studies. After screening, appropriate data were extracted. Meta-analyses utilized the most fully adjusted hazard ratio (HR) with corresponding 95% confidence intervals (CI) as the effect measures. All statistical analyses were performed using R Statistical Software.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The pooled analysis of 29 observational studies showed a significant reduction in lung cancer risk among Metformin users compared with nonusers (HR: 0.85, 95% CI: [0.77–0.94], <i>p</i> = 0.002). Subgroup analyses revealed significant associations in cohort studies (HR: 0.79, 95% CI: [0.70–0.89], <i>p</i> &lt; 0.01) and in studies conducted in Asia (HR: 0.82, 95% CI: [0.68–0.99], <i>p</i> = 0.04). Extended Metformin use (&gt; 3 years) was associated with a significant reduction in lung cancer risk (HR: 0.87, 95% CI: [0.79–0.95]; <i>p</i> &lt; 0.01), whereas no significant effect was observed for shorter durations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This meta-analysis indicated a potential protective effect of Metformin use in individuals with T2DM against lung cancer, with a significant risk reduction observed, particularly among long-term users and in Asian populations. The significant associations identified in cohort studies and in extended-duration use underscore metformin's promise in lung cancer prevention.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"9 8","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cnr2.70651","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148711171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SMAD4 Expression and Its Association With Treatment Resistance and Clinical Outcomes in Oral Squamous Cell Carcinoma Treated With Preoperative Chemoradiotherapy","authors":"Junki Sakata,&nbsp;Akiyuki Hirosue,&nbsp;Ryoji Yoshida,&nbsp;Yuichiro Matsuoka,&nbsp;Yusei Todoroki,&nbsp;Hidetaka Arita,&nbsp;Hikaru Nakashima,&nbsp;Tatsuro Yamamoto,&nbsp;Nozomu Takahashi,&nbsp;Masatoshi Hirayama,&nbsp;Kenta Kawahara,&nbsp;Ryo Toya,&nbsp;Ryuji Murakami,&nbsp;Takaaki Ito,&nbsp;Yoshikazu Kuwahara,&nbsp;Hideki Nakayama","doi":"10.1002/cnr2.70654","DOIUrl":"10.1002/cnr2.70654","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Small mothers against decapentaplegic homologue 4 (SMAD4) plays an important role in transforming growth factor (TGF)-β signaling and is associated with various cancers. However, little is known about SMAD4 expression in oral squamous cell carcinoma (OSCC).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To investigate the clinical and biological significance of SMAD4 expression in OSCC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>Immunohistochemical analysis was performed to detect SMAD4 expression in 90 OSCC specimens obtained from patients who underwent preoperative chemoradiotherapy and surgery (phase II study). We also investigated the correlation between SMAD4 expression and various clinicopathological features. In vitro experiments were performed to assess the effects of SMAD4 expression on chemosensitivity and changes in apoptosis-related molecules. Notably, low SMAD4 expression was significantly correlated with an increased risk of lymph node metastasis, poor response to chemoradiotherapy, and adverse prognosis in patients with OSCC who underwent preoperative 5-FU-based chemoradiotherapy. Additionally, SMAD4 downregulation in OSCC cells decreased sensitivity to cisplatin and 5-fluorouracil and was associated with an increase in cIAP2 expression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The reduced expression of SMAD4 has been linked to both chemotherapy resistance and prognosis in OSCC. However, it may not function as an independent prognostic biomarker. Further research is necessary to determine whether these findings can be generalized to the broader OSCC population.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"9 8","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cnr2.70654","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148711261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Too Old for Surgery? A Case Report of an Octogenarian Patient With Locally Advanced Lung Cancer Achieving Long-Term Survival via Bilobectomy Followed by Adjuvant Targeted Therapy","authors":"Han-Yu Deng,&nbsp;Jia-Hao Li,&nbsp;Xiao-Jun Tang,&nbsp;Qinghua Zhou","doi":"10.1002/cnr2.70652","DOIUrl":"10.1002/cnr2.70652","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>An increasing number of octogenarian patients are being diagnosed with lung cancer, but they are less likely to receive surgery because of fragility. As a result, the optimal management of lung cancer in octogenarians remains unclear. Here we report a case of an octogenarian patient with locally advanced non-small-cell lung cancer (NSCLC) who achieved long-term survival via surgery followed by adjuvant targeted therapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Case</h3>\u0000 \u0000 <p>An 82-year-old male patient was admitted to our center for lung cancer surgery in April 2020 at West China Hospital, Sichuan University. He was clinically diagnosed with cT2N1M0(cIIB, AJCC 8th edition) lung cancer in the right lower lobe. Because of his good cardiopulmonary function without comorbidities, the patient was scheduled for thoracoscopic surgery. However, due to tumor invasion into the middle lobe and dense adhesions to the bronchus and vessels, the patient underwent conversion to open thoracotomy and finally received bilobectomy with systematic lymph node dissection. The patient recovered uneventfully and was discharged on postoperative day 5. After surgery, the patient was pathologically diagnosed with pT3N2M0(pIIIB) lung adenocarcinoma harboring an EGFR L858R gene mutation and began adjuvant icotinib. The patient progressed with multiple pulmonary metastasis at 13 months after starting icotinib and his liquid biopsy revealed a T790M mutation; he began treatment with the third-generation EGFR-TKI aumolertinib. In the last follow-up in December 2025, the patient remained on aumolertinib therapy and remained alive without progression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Age alone is not a contraindication for lung cancer surgery and octogenarian patients may tolerate surgical resection following careful preoperative evaluation. Adjuvant targeted therapy may prolong survival in octogenarian lung cancer patients harboring oncogenic driving gene mutation after surgery.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"9 8","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cnr2.70652","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148705388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting Spatiotemporal Heterogeneity of oncomiRNAs: A New Frontier in Cancer Therapy","authors":"T. Jeethy Ram,&nbsp;Muralee Damodaran","doi":"10.1002/cnr2.70639","DOIUrl":"10.1002/cnr2.70639","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>miRNAs are short RNA transcripts that modulate gene expression after transcription and have emerged as pivotal regulators of cancer biology. A subset, termed oncomiRNAs, functions as oncogenes or tumor suppressors, influencing key cellular events such as cell growth, programmed cell death, neovascularization, tissue invasion, and metastatic spread. Dysregulation of these miRNAs drives tumor initiation and progression, underscoring their role in cancer evolution. Traditionally, studies have relied on bulk tissue analyses, overlooking the profound spatiotemporal heterogeneity of oncomiRNA expression, including variations across tumor regions, metastatic sites, disease stages, and during treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Recent Findings</h3>\u0000 \u0000 <p>Advances in spatial transcriptomics, single-cell profiling, and longitudinal liquid biopsy technologies have provided new insights into the dynamic regulation of oncomiRNAs. These approaches reveal significant spatiotemporal variability in miRNA expression and are increasingly implicated in shaping tumor heterogeneity, therapeutic resistance, immune evasion, and divergent clinical outcomes. Emerging evidence underscores the importance of integrating these dynamic molecular patterns into biomarker discovery frameworks and precision oncology strategies. Furthermore, the incorporation of artificial intelligence and multi-omics data integration is enhancing patient stratification and predictive modeling.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>A comprehensive understanding of the spatiotemporal regulation of oncomiRNAs is essential for advancing next-generation cancer diagnostics and therapeutics. Future efforts should focus on systematic multi-region and longitudinal study designs, as well as their integration into adaptive clinical trials. Leveraging these insights may enable miRNA-guided, stage-adapted precision cancer theranostics in heterogeneous malignancies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"9 8","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13453589/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148700798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}