Translational Oncology最新文献

{"title":"Establishment and characterization of preclinical models of human gynecologic tract carcinosarcomas demonstrates targetable FGFR1 alterations","authors":"Nelson K.Y. Wong ,&nbsp;Marta Llaurado Fernandez ,&nbsp;Hannah Kim ,&nbsp;Pooja Praveen Kumar ,&nbsp;DuPreez Smith ,&nbsp;James Key ,&nbsp;Yen-Yi Lin ,&nbsp;Stanislav Volik ,&nbsp;An Nhien Tong ,&nbsp;Stephane Le Bihan ,&nbsp;Colin C. Collins ,&nbsp;Yangxin Fu ,&nbsp;Hui Xue ,&nbsp;YZ Wang ,&nbsp;Martin Köbel ,&nbsp;Mark S. Carey ,&nbsp;Cheng-Han Lee","doi":"10.1016/j.tranon.2025.102591","DOIUrl":"10.1016/j.tranon.2025.102591","url":null,"abstract":"<div><h3>Objective</h3><div>Gynecologic carcinosarcoma is an uncommon but aggressive malignancy that frequently requires systemic therapy but therapeutic options are limited. Development of preclinical models is therefore important for therapeutic advancement.</div></div><div><h3>Methods</h3><div>Carcinosarcoma tumor (6 uterine and 1 tubo-ovarian) from 7 surgical samples were implanted into immunocompromised mice for patient-derived xenograft (PDX) and/or cell line development. The histologic, immunophenotypic and genetic features were characterized. Based on the observed molecular profiles and targetable molecular alterations, <em>in vivo</em> studies were conducted to evaluate the efficacy of targeted therapy on tumor growth.</div></div><div><h3>Results</h3><div>We established 1 cell line and 6 PDX models which recapitulated the dominant phenotype of the respective parental tumors with preserved mesenchymal differentiation lineage in the sarcomatous component. Genomically, the PDX/cell line models preserved similar complex pattern of copy number alterations and similar mutation landscape when compared to the respective parental tumors. All 7 parental carcinosarcoma tumors and PDX/cell line models harbored pathogenic <em>TP53</em> mutations. Moreover, we identified recurrent copy number gain/amplification involving several receptor tyrosine kinases (RTK), including amplification and protein over-expression of <em>FGFR1. In vivo</em> drug evaluation using a small molecule inhibitor (AZD4547) of FGFRs showed significant growth inhibition in the carcinosarcoma PDX tumor with the highest <em>FGFR1</em> amplification and protein expression whereas AZD4547 showed no significant growth effects on carcinosarcoma lacking high level <em>FGFR1</em> amplification, indicating oncogenic dependency on the amplified RTK pathway.</div></div><div><h3>Conclusions</h3><div>These findings demonstrate the utility of patient-derived tumor models in the identification and the functional validation of potentially targetable molecular alterations in preclinical setting.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"63 ","pages":"Article 102591"},"PeriodicalIF":5.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145471810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a single-cell derived MDSCs signature score for prognostic risk stratification and therapeutic decision guidance in breast cancer","authors":"Jinbao Yin ,&nbsp;Binbin Li ,&nbsp;Hui Xiong ,&nbsp;Jiepeng Gan ,&nbsp;Lan Liang","doi":"10.1016/j.tranon.2025.102605","DOIUrl":"10.1016/j.tranon.2025.102605","url":null,"abstract":"<div><h3>Background</h3><div>Myeloid-derived suppressor cells (MDSCs) function as critical immunosuppressive constituents within the breast cancer tumor microenvironment (TME). However, their molecular variability and clinical translation potential remain inadequately characterized.</div></div><div><h3>Methods</h3><div>By combining single-cell RNA sequencing (scRNA-seq) with bulk multi-omics datasets, we screened and confirmed MDSCs signature genes specific to breast cancer. A prognostic risk scoring model was constructed using machine learning approaches and tested across multiple independent patient cohorts. The model’s predictive capacity for chemotherapy sensitivity, immunotherapy responsiveness, and TME features was systematically assessed.</div></div><div><h3>Results</h3><div>After integrating the single-cell datasets GSE161529 and GSE176078, we identified 12,767 MDSCs along with their 209 characteristic genes. To ensure the reliability of our results, we employed various analytical methods and utilized diverse data for validation. From this signature, a 5-gene risk score model comprising BCL2A1, GDI2, GRINA, RNASE1, and SERPINA1 was constructed, demonstrating robust prognostic stratification with a 1- to 10-year overall survival (OS) AUC exceeding 0.6 and independent predictive value. High-risk patients exhibited characteristic features of an immunosuppressive tumor microenvironment (TME), including increased M2 macrophages and regulatory T cells, alongside diminished cytotoxic T lymphocyte activity. These patients also showed poor responses to both chemotherapy and immunotherapy.</div></div><div><h3>Conclusion</h3><div>This investigation marks the initial systematic characterization of a new MDSCs gene signature in breast cancer, alongside the establishment of an MDSCs-associated marker scoring framework with multi-aspect clinical translation capability, thereby linking MDSCs fundamental biology to precision oncology in this cancer type.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"63 ","pages":"Article 102605"},"PeriodicalIF":5.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145551131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Apolipoprotein C1 functions as a target of thyroid carcinoma and synergistic effects with promising candidate-cyclopamine","authors":"Rui Wang ,&nbsp;Bin Wang ,&nbsp;Juanhong Shi ,&nbsp;Zhi Zhu ,&nbsp;ZhenZhen Yao","doi":"10.1016/j.tranon.2025.102617","DOIUrl":"10.1016/j.tranon.2025.102617","url":null,"abstract":"<div><div>There is an urgent need to identify novel therapeutic targets for papillary thyroid carcinoma (PTC). <em>APOC1</em> (Apolipoprotein C1) has emerged as a candidate: it is overexpressed in several cancers and its high expression often associates with worse clinical outcomes. Using bioinformatic analysis of TCGA-THCA RNA-seq data, we found that <em>APOC1</em> is highly expressed in PTC and that elevated <em>APOC1</em> correlates with poorer patient prognosis and with signatures of immune-evasion. We validated these observations in PTC cell lines. Immunofluorescence, colony-formation assays, CCK-8 proliferation measurements, and flow-cytometry apoptosis analysis all indicate that <em>APOC1</em> promotes proliferation, enhances colony survival, and confers resistance to apoptosis. To identify candidate therapeutics that target <em>APOC1</em>-related pathways, we queried the Connectivity Map using shared differentially expressed genes (DEGs) and nominated cyclopamine as the top small-molecule hit. Cyclopamine reduces PTC cell proliferation and induces apoptosis in vitro; <em>APOC1</em> depletion further sensitizes cells to cyclopamine, producing greater inhibition of proliferation and increased cell death. Finally, cyclopamine suppresses tumor growth in a PTC mouse model. Together, these results implicate <em>APOC1</em> as a driver of PTC progression and immune evasion and identify cyclopamine as a promising therapeutic that acts, at least in part, through <em>APOC1</em>-related signaling. Our study thus provides a rationale for targeting APOC1 as a novel treatment strategy for papillary thyroid carcinoma.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"63 ","pages":"Article 102617"},"PeriodicalIF":5.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145606228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bmi-1 inhibition sensitizes head and neck cancer stem cells to cytotoxic chemotherapy","authors":"Alexandra E. Herzog ,&nbsp;Shirley Zheng ,&nbsp;Kristy A. Warner ,&nbsp;Jaqueline V. Vanini ,&nbsp;Ritu Somayaji ,&nbsp;Madelynn R. Johnson ,&nbsp;Zhaocheng Zhang ,&nbsp;Peter J. Polverini ,&nbsp;Rogério M Castilho ,&nbsp;Alexander T. Pearson ,&nbsp;Jacques E. Nör","doi":"10.1016/j.tranon.2025.102603","DOIUrl":"10.1016/j.tranon.2025.102603","url":null,"abstract":"<div><div>Cancer stem cells (CSC) drive therapeutic resistance and recurrence in head and neck squamous cell carcinoma (HNSCC). We and others have shown that treatment with cytotoxic chemotherapy agents (<em>e.g.</em> Cisplatin, Carboplatin) induce Bmi-1 expression and increase the fraction of highly tumorigenic CSC in HNSCC. Notably, Bmi-1 is a master regulator of stem cell self-renewal and DNA repair. The purpose of this work was to test whether therapeutic inhibition of Bmi-1 sensitizes HNSCC cancer stem cells to chemotherapy. HNSCC cells (UM-SCC-1,-22A,-22B) were treated with Cisplatin or Carboplatin and subjected to stemness analyses to evaluate the impact of Bmi-1 on chemoresistance. We observed that both, shRNA-mediated Bmi-1 silencing or pharmacologic inhibition of Bmi-1 with the small molecule inhibitor PTC596, blocked chemotherapy-induced cancer stemness (<em>i.e.</em> increase in the fraction of ALDH^highCD44^high cells), CSC self-renewal (<em>i.e.</em> orosphere formation) and inhibited protective DNA damage responses in HNSCC. Further, it is known that high IL-6 serum levels correlate with poor HNSCC patient survival, and that platinum-based therapies induce IL-6 signaling. Here, we observed that Bmi-1 silencing (or PTC596 treatment) inhibited the IL-6R/STAT3 signaling pathway even in presence of platinum-based cytotoxic agents (<em>i.e.</em> Cisplatin, Carboplatin). <em>In vivo</em>, Bmi-1 inhibition with PTC596 suppressed Cisplatin-mediated increase in the fraction of ALDH^highCD44^high cells (cancer stemness). Collectively, these preclinical results demonstrate that Bmi-1 is a key mediator of head and neck cancer stemness and suggest that HNSCC patients might benefit from treatment with a Bmi-1 inhibitor combined with a conventional chemotherapeutic agent.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"63 ","pages":"Article 102603"},"PeriodicalIF":5.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145606168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Shaping the future one slice at a time: How 3D organotypic tumour slice models are driving drug discovery in ovarian cancer","authors":"Maria Edwards ,&nbsp;Pablo Caruana ,&nbsp;Mireia Escar ,&nbsp;Maria Virtudes Céspedes","doi":"10.1016/j.tranon.2025.102633","DOIUrl":"10.1016/j.tranon.2025.102633","url":null,"abstract":"<div><div>Despite therapeutic advancements, ovarian cancer remains one of the most lethal gynaecological malignancies, highlighting the urgent need for innovative drug discovery approaches. Traditional 2D cell line models fail to accurately replicate the complexity of the tumour and its microenvironment (TME), leading to suboptimal drug evaluations. Organotypic tumour slice culture (OTSC) has emerged as a promising 3D <em>ex vivo</em> platform that preserves native tissue architecture, cellular interactions, and molecular heterogeneity of the tumour and its TME, providing a more physiologically relevant system for drug testing. This review examines the evolution of OTSC in ovarian cancer and its applications across chemotherapy, targeted therapy, immunotherapy, and virotherapy. We highlight the role of OTSC in identifying predictive biomarkers of drug response, drug resistance mechanisms – including those in the stroma – and elucidating novel therapeutic strategies. While OTSC has demonstrated its ability to rapidly provide insights into patient-specific responses, further integration of advanced multi-omics analyses could enhance its potential as a precision medicine platform. With its 3D heterogenic complexity, OTSC could also facilitate the development and evaluation of TME-directed therapies, novel multitarget drugs, and tumour-targeting drug delivery systems, ultimately shaping the future of ovarian cancer therapy and improving clinical outcomes.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"63 ","pages":"Article 102633"},"PeriodicalIF":5.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145696382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From benchside avatars to bedside breakthroughs: Patient-derived organoids in the new era of cancer immunotherapy","authors":"Zhihui Mi ,&nbsp;Hui Guan ,&nbsp;Guodong Zhang ,&nbsp;Dongyang Li ,&nbsp;Yang Yu ,&nbsp;Jialin Qu","doi":"10.1016/j.tranon.2025.102619","DOIUrl":"10.1016/j.tranon.2025.102619","url":null,"abstract":"<div><div>The success of cancer immunotherapy is hampered by the lack of dynamic models that can predict patient-specific responses and guide the development of novel treatments. Static biomarkers, such as PD-L1 expression and tumor mutational burden, often fail to capture the complexity of the tumor-immune dialogue. Patient-derived tumor organoids (PDTOs) have emerged as a revolutionary ex vivo platform that bridges this gap. This review outlines the evolution of PDTOs from simple epithelial cultures to sophisticated, immune-competent \"avatars\" that faithfully recapitulate the patient's tumor microenvironment (TME). We critically discuss the key methodologies for reconstructing the TME, including \"add-in\" co-culture systems with diverse immune and stromal cells (e.g., T-cells, MDSCs, CAFs, neutrophils) and \"all-in-one\" approaches that preserve the native immune ecosystem. Furthermore, we highlight the expanding role of these advanced models beyond predicting checkpoint inhibitor efficacy. We showcase their groundbreaking applications as core development platforms for next-generation immunotherapies, including CAR-T cell therapy and the validation of personalized neoantigen-based vaccines. While acknowledging the significant translational challenges that remain, we conclude that immune-competent PDTOs represent an indispensable tool poised to accelerate the new era of precision immuno-oncology.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"63 ","pages":"Article 102619"},"PeriodicalIF":5.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145661742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Radiotherapy in the management of PDAC, from past to present","authors":"Julie Dardare ,&nbsp;Nicolas Martz ,&nbsp;Andréa Witz ,&nbsp;Margaux Betz ,&nbsp;Cassandra Michel ,&nbsp;Pauline Gilson ,&nbsp;Jean-Louis Merlin ,&nbsp;Aurélien Lambert ,&nbsp;Alexandre Harle","doi":"10.1016/j.tranon.2025.102632","DOIUrl":"10.1016/j.tranon.2025.102632","url":null,"abstract":"<div><div>Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal forms of cancer, with a dismal survival rate. Therapeutic options are restricted in surgery for patients with resectable disease and in chemotherapy for those with unresectable disease. The potential benefits of radiotherapy (RT) or chemoradiotherapy (CRT) have been extensively investigated in both neoadjuvant and adjuvant settings in the management of patients with PDAC. Nevertheless, a substantial number of clinical trials have yielded conflicting findings, thereby rendering the impact of RT on patient survival and margin-negative (R0) resection inconclusive. A comprehensive examination of the historical evolution of RT in PDAC, encompassing the identification of both constraints and opportunities for advancement, is essential to establish RT as a promising therapeutic avenue for patients with PDAC. The aim of this review is to provide a synthesis of past clinical trials and future studies to elucidate the evolving role of RT in the management of PDAC as adjuvant and neoadjuvant CRT across different stages of the disease.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"63 ","pages":"Article 102632"},"PeriodicalIF":5.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145715884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The new Bruton’s tyrosine kinase inhibitors SPA8007 and SPA8009 reduce stemness and invasiveness of patient-derived glioblastoma tumorspheres","authors":"Euna Jo ,&nbsp;Eun Lee ,&nbsp;Yoojung Oh ,&nbsp;Dongkyu Lee ,&nbsp;Byungho Lee ,&nbsp;Kibyeong Kim ,&nbsp;Ran Joo Choi ,&nbsp;Jiyun Hong ,&nbsp;Yuesong Jeon ,&nbsp;Hyewon Cho ,&nbsp;Yong-Sung Choi ,&nbsp;Sangwoo Kim ,&nbsp;So Young Won ,&nbsp;Seonah Choi ,&nbsp;Tae Hoon Roh ,&nbsp;Ju Hyung Moon ,&nbsp;Eui Hyun Kim ,&nbsp;Jong Hee Chang ,&nbsp;Raok Jeon ,&nbsp;Seok-Gu Kang","doi":"10.1016/j.tranon.2025.102585","DOIUrl":"10.1016/j.tranon.2025.102585","url":null,"abstract":"<div><div>Glioblastoma (GBM), the most prevalent primary brain tumor, remains incurable due to the presence of cancer stem cells (CSCs), which can be isolated as tumorspheres (TSs) that exhibit classical characteristics of CSCs, including stemness and invasiveness. The significantly elevated expression of Bruton’s tyrosine kinase (BTK) in GBM tissues identifies BTK as a potential therapeutic target in GBM. Consequently, ibrutinib, an FDA-approved BTK inhibitor for hematological malignancies, has been repurposed as a candidate for GBM treatment, demonstrating inhibitory effects on the proliferation, stemness, and invasiveness of GBM cell lines and TSs. However, its broad-spectrum activity targeting other Tec family kinases and members of the epidermal growth factor receptor family, poses potential life-threatening risks, necessitating the development of more selective alternatives. To address this shortcoming, we synthesized BTK-selective analogs (SPA1758, SPA1763, SPA8004, SPA8007, and SPA8009) specifically designed to target two hallmark features of GBM TSs: stemness and invasiveness.</div><div>WST and ATP assays identified SPA8007 and SPA8009 as the most effective candidates with superior cytotoxic effects in TSs. Additionally, both SPA8007 and SPA8009 significantly inhibited neurosphere formation and reduced invasiveness in GBM TSs. Furthermore, SPA8007 demonstrated improved survival rates in a GBM xenograft mouse model and significantly reduced the expression of invasiveness markers, as observed in immunohistochemistry analysis. These findings highlight SPA8007 as a potential novel chemotherapeutic agent with high specificity and efficacy to enhance GBM therapy.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"63 ","pages":"Article 102585"},"PeriodicalIF":5.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145365714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of cuproptosis-related subtypes, construction of a prognosis model, and tumor microenvironment landscape in multiple myeloma","authors":"Li Xu ,&nbsp;Hui Zhang ,&nbsp;Kai Wang ,&nbsp;Xuejie Gao ,&nbsp;Wenxuan Bu ,&nbsp;Dandan Yu ,&nbsp;Ke Hu ,&nbsp;Qikai Zhang ,&nbsp;Guanli Wang ,&nbsp;Xiaosong Wu ,&nbsp;Xinyan Jia ,&nbsp;Yu Peng ,&nbsp;Dongliang Song ,&nbsp;Hongfei Yi ,&nbsp;Haiyan Cai ,&nbsp;Jumei Shi ,&nbsp;Qilin Feng","doi":"10.1016/j.tranon.2025.102601","DOIUrl":"10.1016/j.tranon.2025.102601","url":null,"abstract":"<div><div>Multiple myeloma (MM) is a challenging hematologic malignancy with increasing incidence. Cuproptosis, a copper-dependent form of cell death associated with mitochondrial metabolism and protein lipoylation, remains unexplored in MM. This study aims to investigate this connection using transcriptome profiling and clinical data from the Gene Expression Omnibus database. Analysis of copper death-related genes (CRGs) revealed significant expression differences in 6 out of 12 CRGs, with GLS, ATP7B, PDHA1, MTF1, CDKN2A and DLAT showing notable correlations with survival of MM patients. Unsupervised clustering identified two cuproptosis molecular subtypes in MM patients, which exhibited significant associations with clinical features, prognosis, and immune cell infiltration. These subtypes identified 186 potential MM target genes, enriched in protein binding and intracellular/extracellular structure regulations. Five key biomarkers (CKS2, HGF, HSP90B1, PRIM1, and VCAM1) effectively stratified patients into high- and low-risk groups, strongly correlated with age, ISS stage, serum LDH content, and survival. Functional enrichment analysis revealed differential genes were involved in regulating cell membrane structure, protein binding, and metabolic pathways. High- and low-risk groups displayed distinct immune cell infiltration patterns and immune checkpoint expressions. In vitro experiments, the combination of elesclomol (a copper ion carrier) and bortezomib (Bortezomib) demonstrated a synergistic anti-myeloma effect through excessive intracellular reactive oxygen species generation. This study provides valuable insights into the role of CRGs in MM, potentially aiding in prognosis prediction and the development of effective, personalized therapeutic strategies.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"63 ","pages":"Article 102601"},"PeriodicalIF":5.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145528922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Utilization of ultrasound combined with Ki-67 and CESM quantitative parameters to predict pathological complete response following neoadjuvant chemotherapy in triple-negative breast cancer","authors":"YanYan Zhang ,&nbsp;Mei Qin Yuan ,&nbsp;Tian Li Jia ,&nbsp;Jing Guo","doi":"10.1016/j.tranon.2025.102589","DOIUrl":"10.1016/j.tranon.2025.102589","url":null,"abstract":"<div><h3>Objective</h3><div>To evaluate the predictive value of ultrasound parameters combined with Ki-67 and contrast-enhanced spectral mammography (CESM) for assessing pathological complete response (pCR) following neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC).</div></div><div><h3>Methods</h3><div>This retrospective study included 78 TNBC patients who underwent surgery after NAC and were stratified into pCR and non-pCR (nPCR) groups based on postoperative pathology. Baseline ultrasound imaging was conducted upon admission. Primary tumor ultrasound features and change rates in tumor longest diameter (△D2, △D4) after 2 and 4 NAC cycles were analyzed. CESM was performed pre-treatment and after two cycles to calculate △CNR (percentage reduction in relative enhancement grayscale value). Univariate and multivariate logistic regression analyses were employed to identify independent predictors of pCR.</div></div><div><h3>Results</h3><div>Univariate analysis revealed significant differences in △D2, △D4, retromammary space disappearance, Ki-67 expression, and △CNR between the pCR and nPCR groups following 2 and 4 cycles (<em>P</em> <em>&lt;</em> 0.05). Variables with <em>P</em> <em>&lt;</em> 0.05 were included in multivariate binary logistic regression. △D4, △CNR, and Ki-67 were identified as independent predictors of pCR in TNBC (OR=1.064, <em>P</em> <em>=</em> 0.041; OR=1.081, <em>P</em> <em>=</em> 0.016; OR=0.140, <em>P</em> <em>=</em> 0.005, respectively). The combined predictive model yielded an AUC of 0.869 (95 % CI: 0.774–0.963), with a sensitivity of 84.0 % and specificity of 84.9 %.</div></div><div><h3>Conclusion</h3><div>The integration of △D4, △CNR, and Ki-67 offers clinical utility in predicting NAC response in TNBC.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"63 ","pages":"Article 102589"},"PeriodicalIF":5.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145453150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}