Cancer reports最新文献

{"title":"Paraneoplastic Myopathy as a Possible Initial Presentation of Sporadic Burkitt Lymphoma in an Immunocompetent Adult: A Case Report","authors":"Abolfazl Khalafi-Nezhad,&nbsp;Dena Firouzabadi,&nbsp;Vahid mohammadkarimi,&nbsp;Amirreza Dehghanian","doi":"10.1002/cnr2.70669","DOIUrl":"10.1002/cnr2.70669","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Burkitt's lymphoma (BL) is a highly aggressive B-cell non-Hodgkin lymphoma with rapid proliferation and early systemic dissemination. Neuromuscular manifestations are rare and are typically secondary to direct infiltration or metabolic complications. Paraneoplastic myopathy as the initial presentation of BL is exceedingly uncommon, particularly in immunocompetent adults.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Case Presentation</h3>\u0000 \u0000 <p>We report the case of an immunocompetent adult male who presented with acute progressive proximal muscle weakness and markedly elevated creatine phosphokinase (CPK) levels. Extensive autoimmune, metabolic, and endocrine evaluations were unremarkable. Electrophysiological studies supported a primary myopathic process. Contrast-enhanced computed tomography revealed left axillary lymphadenopathy and splenomegaly without generalized lymphadenopathy. Excisional lymph node biopsy confirmed sporadic Burkitt's lymphoma with MYC rearrangement. Muscle biopsy was deferred due to rapid disease progression and the urgent need for oncologic treatment. The patient was treated with the Hyper-CVAD regimen combined with rituximab and central nervous system prophylaxis. Following chemotherapy, muscle strength improved rapidly, accompanied by a marked decline in serum CPK levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This case highlights a rare paraneoplastic manifestation of Burkitt's lymphoma presenting as acute myopathy. Rapid clinical and biochemical response to chemotherapy supports a tumor-mediated mechanism. Clinicians should consider underlying hematologic malignancy in patients with unexplained myopathy and elevated muscle enzymes, as early diagnosis and prompt treatment may significantly improve outcomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"9 9","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13534003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148872959","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":"Comprehensive In Silico Analysis Identifies MSTO1 and LIG1 as Candidate Biomarkers With Diagnostic and Prognostic Relevance in Hepatocellular Carcinoma.","authors":"Jana Hamad, Hussein Fayyad-Kazan, Fadi Abdel-Sater","doi":"10.1002/cnr2.70685","DOIUrl":"10.1002/cnr2.70685","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and remains a major cause of cancer-related mortality worldwide. Its poor clinical outcomes are largely attributed to late-stage diagnosis and the limited accuracy of currently available diagnostic and prognostic biomarkers. Therefore, identifying novel molecular markers with improved sensitivity, specificity, and therapeutic relevance is essential for enhancing early detection and guiding personalized treatment strategies.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Aims: &lt;/strong&gt;To identify and prioritize novel candidate HCC biomarkers with diagnostic and prognostic value and potential therapeutic vulnerability using integrated multi-omics, survival, functional dependency, and tumor microenvironment analyses.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods and results: &lt;/strong&gt;We examined the mRNA and protein expression levels of 8 DEGs in HCC tissues in the TCGA and CPTAC datasets using UALCAN, which showed that MSTO1 and LIG1 were overexpressed consistently in HCC relative to normal liver tissues. Moreover, elevated expression levels of these genes were significantly associated with higher tumor grade and advanced stage. Kaplan-Meier plotter survival data confirmed that increased expression of MSTO1 and LIG1 was associated with poorer overall survival. The DepMap CRISPR knockout data confirmed a functional dependency of both genes in HCC cell lines. CBioPortal analyses provided characterization of genomic alterations and enabled enrichment analysis of co-expressed genes, and the TCGA-UALCAN pan-cancer analyses supported the assessment of tissue specificity across tumor types. TIMER3 analyses linked candidate gene expression with immune cell infiltration patterns. Diagnostic performance by ROC analysis showed excellent discrimination for MSTO1 (AUC = 0.987) and good discrimination for LIG1 (AUC = 0.897). Multivariate Cox regression with Benjamini-Hochberg FDR correction across the eight genes supported MSTO1 as a candidate independent prognostic factor after adjustment for tumor stage, grade, etiology, age, and sex (HR = 1.29, p = 0.035), whilst LIG1 showed no independent prognostic value. Promoter methylation of MSTO1 and ADH4, assessed via UALCAN, showed that both genes were significantly differentially methylated in the promoter region of primary HCC tissues compared with normal liver tissues. Our study also confirmed the biological and clinical relevance of established HCC biomarkers: TERT, IRAK1, and ADH4.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;MSTO1 and LIG1 emerged as candidate diagnostic biomarkers in HCC. Additionally, MSTO1 showed a candidate prognostic association with overall survival that remained significant after adjusting for tumor stage, grade, and etiology, as well as patients' age, but not after further adjustment for AFP status. Functional data also highlighted MSTO1 as a candidate therapeutic dependency. On the other hand, LIG1 showed no independent prognostic association in","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"9 9","pages":"e70685"},"PeriodicalIF":2.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13572204/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148963069","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":"Comprehensive Profiling of ac4C RNA Modification Identifies CERCAM in Cancer-Associated Fibroblasts as a Key Prognostic and Microenvironmental Regulator in Colorectal Cancer.","authors":"Yang Xia, Jialin Dai, Xinyi Zhou, Ruige Zhang","doi":"10.1002/cnr2.70677","DOIUrl":"10.1002/cnr2.70677","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;N4-acetylcytidine (ac4C) RNA modification has emerged as a critical epigenetic regulator in tumorigenesis and progression. However, the comprehensive landscape of ac4C modification in colorectal cancer (CRC), particularly its orchestration of the tumor microenvironment (TME) and stromal crosstalk, remains largely unexplored.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Aims: &lt;/strong&gt;This study aimed to comprehensively delineate the landscape of N4-acetylcytidine (ac4C) RNA modification in colorectal cancer (CRC) to uncover its role in shaping the tumor microenvironment and clinical outcomes. Integrated bioinformatic and in vitro analyses revealed that ac4C patterns dictate aggressive stromal crosstalk and identified CERCAM as a cancer-associated fibroblast (CAF)-specific driver of tumor progression, providing a novel framework for prognostic prediction and personalized targeted therapy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Transcriptomic and clinical data of CRC patients were curated from TCGA and GEO databases (GSE14333, GSE17536, GSE38832, GSE39582). The ac4C modification patterns were quantified using single-sample Gene Set Enrichment Analysis (ssGSEA). Single-cell RNA sequencing (scRNA-seq) analyses were performed via the scCancer Explorer database. A prognostic ac4C score was constructed to evaluate clinical outcomes and therapeutic vulnerabilities. The functional role of the identified target gene, CERCAM, was validated using in vitro co-culture experiments.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Patients with high ac4C scores exhibited worse prognosis, higher clinical stages, and metastasis (N2, M1). High ac4C levels positively correlated with epithelial-mesenchymal transition (EMT), TGF-β signaling, and extracellular matrix (ECM) receptor interactions, whereas low ac4C levels were associated with cell cycle, fatty acid metabolism, and microsatellite stability (MSS). The TME of high-ac4C tumors was characterized by higher Stromal, Immune, and ESTIMATE scores, elevated immune checkpoints (LAG3, CD14, LILRB2, SIRPA, CD8A), and strong correlations with macrophages and NK cells. scRNA-seq analysis revealed that CERCAM, a key gene within the ac4C network, was predominantly expressed in cancer-associated fibroblasts (CAFs) rather than tumor cells. DNA methylation of CERCAM was significantly elevated in metastatic CRC compared to primary tumors. In vitro experiments confirmed that CERCAM was overexpressed in CAFs and CRC tissues. Co-culturing CRC cells (RKO, HCT116) with CERCAM-knockdown CAFs significantly suppressed tumor cell proliferation, migration, and invasion. Furthermore, the ac4C score effectively predicted tumor mutational landscape differences and sensitivities to agents like pazopanib, gefitinib, and conventional chemotherapies.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;This study delineates the crucial role of ac4C modification in shaping the CRC microenvironment, identifies CERCAM as a CAF-specific driver of tumor progression, and provides a transl","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"9 9","pages":"e70677"},"PeriodicalIF":2.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13598370/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149023792","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":"A Review of Senescence-Associated Secretory Phenotype-Mediated Remodeling of the Tumor Microenvironment: Implications for Cancer Progression and Therapy.","authors":"Sneha Pallatt, Sibin Nambidi, Antara Banerjee, Surajit Pathak","doi":"10.1002/cnr2.70682","DOIUrl":"10.1002/cnr2.70682","url":null,"abstract":"<p><strong>Background: </strong>Cellular senescence influences cancer progression through irreversible cell-cycle arrest, immune surveillance, and paracrine signaling mediated by the senescence-associated secretory phenotype (SASP). SASP comprises inflammatory cytokines, chemokines, growth factors, and matrix-remodeling enzymes that regulate the tumor microenvironment (TME).</p><p><strong>Objective: </strong>This review describes the current evidence on the mechanisms of SASP induction, its condition-dependent roles in cancer, TME remodeling, and emerging strategies targeting senescent cells and SASP signaling.</p><p><strong>Methods: </strong>Relevant literature was identified through searches on PubMed, Scopus, Web of Science, and Google Scholar using keywords related to cellular senescence, SASP, cancer, TME, senolytics, and senomorphics. Peer-reviewed English-language studies published primarily between January 2000- March 2026 were considered, including preclinical (in vitro, in vivo), and clinical studies investigating SASP induction and regulation, its role in cancer progression and TME remodeling, and therapeutic strategies targeting senescent cells or SASP signaling.</p><p><strong>Interpretation of the retrieved articles: </strong>SASP exhibits both tumor-suppressive and tumor-promoting activities depending on cellular and tissue condition. While transient SASP may enhance antitumor immunity and suppress early tumorigenesis, persistent SASP, particularly during therapy-induced senescence (TIS), can promote tumor growth, angiogenesis, immune evasion, cancer stemness, metastasis, and therapeutic resistance. Senolytics and senomorphics have therefore emerged as promising approaches for targeting senescent cells and their detrimental secretory effects. SASP-associated molecules also show potential as biomarkers, although specificity and tissue-dependent heterogeneity remain major challenges.</p><p><strong>Conclusion: </strong>Current evidence supports SASP as a major regulator of the TME and an important determinant of cancer progression and therapeutic response. Understanding the condition-dependent functions of SASP is critical for developing effective senescence-targeted cancer therapies.</p>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"9 9","pages":"e70682"},"PeriodicalIF":2.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13572038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148963098","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":"Prospective Phase II Trial of Biweekly Gemcitabine Plus Nab-Paclitaxel as First-Line Therapy in Patients Aged 75 Years and Older With Unresectable Pancreatic Cancer.","authors":"Kenji Ikezawa, Toshihiro Imai, Ryoji Takada, Takuo Yamai, Nobuyasu Fukutake, Makiko Urabe, Yugo Kai, Kaori Mukai, Tasuku Nakabori, Kazuyoshi Ohkawa","doi":"10.1002/cnr2.70691","DOIUrl":"10.1002/cnr2.70691","url":null,"abstract":"<p><strong>Background: </strong>Although older adults (≥ 75 years) constitute a large proportion of patients with unresectable pancreatic cancer (PC), they remain underrepresented in clinical trials. Biweekly gemcitabine plus nab-paclitaxel (GnP) has been evaluated in retrospective studies as an alternative dosing schedule, whereas prospective evidence remains limited.</p><p><strong>Aims: </strong>This single-center, prospective Phase II trial aimed to evaluate the efficacy and safety of biweekly GnP as a first-line therapy in older adults with unresectable PC.</p><p><strong>Methods and results: </strong>Eligible patients aged ≥ 75 years with histologically or cytologically confirmed unresectable pancreatic adenocarcinoma received GnP (1000 mg/m² gemcitabine; 125 mg/m² nab-paclitaxel) on days 1 and 15 of each 28-day cycle. The primary endpoint was the overall response rate (ORR). Key secondary endpoints included overall survival (OS), progression-free survival (PFS), and safety. A total of 17 patients were enrolled between August 2019 and March 2021 (median age, 77 years; 13 metastatic, 4 locally advanced). The ORR was 47.1% (8/17; 95% confidence interval [CI], 23.0%-72.2%), and the disease control rate was 82.4% (14/17). The median OS and PFS were 16.8 (95% CI, 5.9-24.6) and 8.3 (95% CI, 4.9-10.1) months, respectively. The 1- and 2-year survival rates were 58.8% and 29.4%, respectively. Grade ≥ 3 hematologic adverse events occurred in 17.6% of patients. Treatment-related adverse events led to treatment discontinuation in three patients: one case of interstitial pneumonia and two cases of peripheral sensory neuropathy. No treatment-related deaths occurred.</p><p><strong>Conclusion: </strong>Biweekly GnP showed promising antitumor activity in a selected population of patients aged ≥ 75 years with unresectable PC. Because enrollment ended before the planned sample size was reached, the study findings should be interpreted cautiously.</p><p><strong>Trial registration: </strong>jRCTs051190038.</p>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"9 9","pages":"e70691"},"PeriodicalIF":2.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13574539/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148966607","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":"Diffuse-Type Tenosynovial Giant Cell Tumor of the Hip With Acetabular Bone Involvement: A Case Report With Radiologic-Pathologic Correlation.","authors":"Wang Quanbing, Xing Huanhuan, Zhang Xing, Yang Tao, Zhang Jun, Zhu Lei, Li Kai, Luo Lei, Ao Feng, Yang Wei","doi":"10.1002/cnr2.70696","DOIUrl":"10.1002/cnr2.70696","url":null,"abstract":"<p><strong>Background: </strong>Diffuse-type tenosynovial giant cell tumor (D-TGCT) is an uncommon synovial neoplasm. Hip involvement is rare and may be difficult to recognize because symptoms are nonspecific and osseous erosion can mimic more aggressive infectious, inflammatory, or neoplastic processes. We report a case of hip D-TGCT that presented as an erosive acetabular lesion and required histopathologic and immunohistochemical confirmation.</p><p><strong>Case: </strong>A 56-year-old man presented with acute right hip pain and restricted motion after a recent febrile illness that had partially improved following empirical intravenous cefuroxime therapy. Magnetic resonance imaging (MRI) demonstrated diffuse intra-articular synovial proliferation with heterogeneous low-to-intermediate signal intensity on T1-weighted images, heterogeneous signal intensity on T2-weighted images, and heterogeneous enhancement after contrast administration. Computed tomography (CT) showed joint effusion and thinning and erosion of the anterior and inferomedial acetabular wall, whereas plain radiographs were unremarkable. Because the imaging and laboratory findings were inconclusive, the patient underwent surgical excision and synovectomy, curettage of the eroded acetabular wall, alcohol ablation, and autologous iliac bone grafting. Histopathologic examination demonstrated mononuclear cells, osteoclast-like multinucleated giant cells, foamy histiocytes, chronic inflammatory cells, and abundant hemosiderin deposition. Integration of the characteristic morphology, diffuse intra-articular growth pattern, imaging findings, and supportive immunohistochemistry established the diagnosis of D-TGCT. Microbiologic cultures were negative. No postoperative radiotherapy was administered. At the 6-month follow-up, the patient reported sustained pain relief and improved hip motion, although mild restriction of motion persisted.</p><p><strong>Conclusion: </strong>Hip D-TGCT should be considered when an intra-articular hip lesion shows synovial proliferation with acetabular erosion, even when inflammatory findings raise concern for alternative diagnoses. Magnetic resonance imaging and computed tomography are complementary for defining soft-tissue extent and osseous involvement, but definitive diagnosis depends on clinicopathologic correlation. This case highlights the diagnostic value of histopathology and immunohistochemistry in destructive-appearing hip lesions.</p>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"9 9","pages":"e70696"},"PeriodicalIF":2.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13589170/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149001235","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":"AZD6738 (Ceralasertib) Enhances Trifluridine's Antitumor Effect in 5-FU–Resistant Colorectal Cancer Cells","authors":"Shuhei Uehara,&nbsp;Takuya Suzuki,&nbsp;Junki Kato,&nbsp;Hiroyuki Asai,&nbsp;Akira Kato,&nbsp;Shinnosuke Harata,&nbsp;Hajime Ushigome,&nbsp;Yushi Yamakawa,&nbsp;Takahisa Hirokawa,&nbsp;Hiroki Takahashi,&nbsp;Yoichi Matsuo,&nbsp;Shuji Takiguchi","doi":"10.1002/cnr2.70668","DOIUrl":"https://doi.org/10.1002/cnr2.70668","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Resistance to 5-fluorouracil (5-FU) remains a major obstacle in colorectal cancer (CRC) treatment. Trifluridine (FTD), the active component of TAS-102, exerts cytotoxicity through DNA incorporation and reportedly remains active in 5-FU-resistant tumors, though with limited clinical efficacy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>We investigated whether AZD6738, an inhibitor of ataxia telangiectasia and Rad3-related kinase (ATR) that regulates the G2/M checkpoint, could enhance FTD efficacy in 5-FU-resistant CRC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>Parental and 5-FU-resistant HCT116 (p53 wild-type) and DLD-1 (p53 mutant-type) sublines were evaluated using WST-1 viability assays, flow cytometry, and immunoblotting for γH2AX, cleaved caspase-3, and p-Chk1 (Ser345). Antitumor efficacy and safety of TAS-102 + AZD6738 were examined in a DLD-1/5FUR xenograft model by measuring tumor volumes and weights, body and organ weights, blood counts, and γH2AX immunohistochemistry. A noncytotoxic AZD6738 concentration significantly enhanced FTD cytotoxicity across a wide concentration range in both parental and resistant cells. The combination increased γH2AX and cleaved caspase-3 while suppressing FTD-induced Chk1 phosphorylation, findings consistent with increased DNA damage and apoptosis following pharmacological treatment with AZD6738. Flow cytometry analysis revealed that AZD6738 abrogated FTD-induced G2/M arrest. In vivo, TAS-102 + AZD6738 significantly suppressed tumor growth compared with monotherapy without increasing hematologic or systemic toxicity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>AZD6738 enhances the antitumor activity of FTD in preclinical models of 5-FU-resistant CRC and is associated with increased DNA damage and apoptosis. These findings provide proof-of-concept supporting further mechanistic and translational investigation of this combination.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"9 9","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cnr2.70668","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148942110","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":"Age-Associated Four-Gene Prognostic Signature in Breast Cancer","authors":"Shiro Uchida","doi":"10.1002/cnr2.70670","DOIUrl":"10.1002/cnr2.70670","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Young-onset breast cancer is associated with inferior disease-free survival (DFS), but the contribution of additional molecular heterogeneity remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To identify an exploratory age-associated gene expression signature linked to recurrence-related outcomes and evaluate its prognostic association.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>We analyzed clinicopathological and RNA-sequencing data from 821 patients with Stages I–III invasive ductal or lobular carcinoma in The Cancer Genome Atlas, including 142 patients aged ≤ 45 years. Genes associated with both age and DFS were screened, followed by LASSO-Cox and stepwise multivariable Cox regression. A four-gene signature (Sig4: C4orf14 [NOA1], LINC01124, ZNF704, and AGFG2) was identified. Young patients had significantly worse DFS than older patients, whereas overall and disease-specific survival did not differ significantly. After adjustment for clinicopathological factors, young age remained associated with worse DFS. Following inclusion of the continuous Sig4 score, the age association was attenuated and no longer statistically significant, while Sig4 remained independently associated with worse DFS. Sig4-high tumors were enriched for proliferation, cell-cycle, DNA-repair, metabolic, and stress-response pathways. In METABRIC, the fixed TCGA-derived Sig4 score was associated with worse relapse-free survival in the overall cohort but not in patients aged ≤ 45 years.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Sig4 is an exploratory age-associated four-gene signature with potential general prognostic relevance in breast cancer. Its utility for risk stratification specifically in young-onset breast cancer was not externally validated and requires confirmation in independent prospective cohorts enriched for young patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"9 9","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13533818/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148872867","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":"Durable Intracranial Response to Sacituzumab Tirumotecan in HER2-Negative Salivary Duct Carcinoma With High TROP2 Expression: A Case Report.","authors":"Guang-Liang Chen, Biao Tan, Sufen Cao, Xin Liu, Yanjing Guo, Dongmei Ji","doi":"10.1002/cnr2.70676","DOIUrl":"10.1002/cnr2.70676","url":null,"abstract":"<p><strong>Background: </strong>Salivary duct carcinoma is an aggressive salivary gland malignancy in which systemic therapy is often guided by androgen receptor and HER2 status. Treatment options are limited for HER2-negative disease after progression on androgen-deprivation therapy and chemotherapy, particularly when active central nervous system (CNS) involvement develops.</p><p><strong>Case: </strong>A 62-year-old man with androgen receptor-positive, HER2-negative salivary duct carcinoma developed progressive intracranial dural metastases involving the left temporal and occipital regions after surgery, adjuvant radiotherapy, androgen-deprivation therapy, and multiple chemotherapy-based regimens. The dominant lesion was a 33.6-mm left temporal dural-based mass extending across the left tentorial leaflet. Immunohistochemical profiling of archival primary tumor tissue showed high membranous TROP2 expression (H-score, 230). Off-label sacituzumab tirumotecan was initiated at 350 mg every 2 weeks without concurrent corticosteroids or local CNS-directed therapy. Serial magnetic resonance imaging demonstrated sustained regression of the dominant left temporal mass from 33.6 to 15.3 mm (-54.5%), with no new intracranial lesions. Intracranial disease control was maintained for approximately 9 months. Treatment-related Grade 2 oral mucositis and leukopenia improved with supportive care and did not require dose reduction or treatment discontinuation.</p><p><strong>Conclusion: </strong>In heavily pretreated, HER2-negative salivary duct carcinoma with high TROP2 expression and progressive intracranial dural metastases, sacituzumab tirumotecan was associated with a durable intracranial response without local CNS-directed therapy. This observation supports further clinical evaluation of TROP2-directed antibody-drug conjugates in salivary duct carcinoma with CNS involvement, while the predictive value of TROP2 expression remains to be established.</p>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"9 9","pages":"e70676"},"PeriodicalIF":2.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13593920/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015674","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":"Survival Outcomes With Cadonilimab Versus PD-(L)1 Therapy in Front-Line Gastric Cancer: A Network Meta-Analysis.","authors":"Zi-Kun Yu, Jia-Hong Yi, Ju Xue, Yu-Chen Huang, Yue Zhao, Chang Jiang, Chen-Xi Yin, Biao Xia, Yi-Xin Zhou, Wen-Zhuo He, Liang-Ping Xia","doi":"10.1002/cnr2.70672","DOIUrl":"10.1002/cnr2.70672","url":null,"abstract":"<p><strong>Background: </strong>The FDA Oncologic Drugs Advisory Committee (ODAC) highlighted that the risk-benefit profile for patients with low PD-L1 expression remains unclear in front-line treatment of HER2-negative gastric and gastroesophageal junction (GC/GEJ) cancer with PD-(L)1 therapy. The first PD-1/CTLA-4 bispecific antibody (BsAb), cadonilimab, has been approved, but it is unknown if it can extend the PD-(L)1 regimen to lower PD-L1 patients.</p><p><strong>Aims: </strong>To indirectly compare the survival outcomes of cadonilimab versus PD-(L)1 therapy in first-line HER2-negative gastric and gastroesophageal junction cancer, with particular focus on patients with low PD-L1 expression, using a network meta-analysis.</p><p><strong>Methods: </strong>Randomized controlled trials with ICIs as first-line treatment were searched in public databases and FDA ODAC up to December 31, 2024. A network meta-analysis was conducted to evaluate the efficacy and safety of approved ICI-based treatments to refine the optimal approach for front-line GC/GEJ.</p><p><strong>Results: </strong>A total of 7127 patients from eight Phase III trials were included. All ICIs-based therapies significantly improved overall survival (OS) compared to chemotherapy. In indirect comparisons, cadonilimab plus XELOX was associated with numerically more favorable OS (HR = 0.78, 95% CI: 0.62-0.98) compared with PD-(L)1 inhibitors. Numerical trends toward longer survival were observed across subgroups, including patients with PD-L1 < 10 (HR = 0.77, 95% CI: 0.58-1.01) and liver metastasis (HR = 0.67, 95% CI: 0.49-0.93), both historically considered immunotherapy-insensitive populations. All ICIs improved PFS compared to chemotherapy. Cadonilimab was associated with numerically better PFS versus PD-(L)1 inhibitors in indirect comparisons (HR = 0.70, 95% CI: 0.57-0.86). The safety analysis showed no significant increase in severe adverse events.</p><p><strong>Conclusions: </strong>In this indirect comparison, cadonilimab showed more favorable survival outcomes versus PD-(L)1 inhibitors in first-line GC/GEJ. Subgroup benefits were observed in liver metastasis, while the PD-L1 < 10 subgroup showed numerical trends. These results highlight the importance of selecting appropriate ICIs to optimize outcomes.</p>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"9 9","pages":"e70672"},"PeriodicalIF":2.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13577937/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148976029","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}