Cancer Biology & Therapy最新文献

{"title":"Prolonged intratumoral treatment with TLR7/8 agonist R848 regulates the tumor immune microenvironment resulting in enhanced antitumor activity.","authors":"Yue Zhang, Xueyi Sun, Shixuan Cheng, Siyu Qian, Na Wan, Fengyun Xing, Hongwen Li, Hang Gu, Zeyuan Wang, Meng Dong, Zhenzhen Yang, Shaoxuan Wu, Mingzhi Zhang, Zhiqiang Han, Xudong Zhang, Huitao Liu, Qingjiang Chen","doi":"10.1080/15384047.2026.2670801","DOIUrl":"10.1080/15384047.2026.2670801","url":null,"abstract":"<p><strong>Background: </strong>Toll-like receptor 7/8 agonists (TLR7/8a), such as resiquimod (R848), are highly potent in activating dendritic cells and thus hold promise for T cell-mediated tumor immunotherapies. However, the short half-life of these small molecules in the lesion and the associated systemic immunotoxicity post-leakage of the drug into the circulation make their clinical application challenging.</p><p><strong>Materials: </strong>To overcome these shortcomings, we tested prolonged TLR7/8a therapy by intratumoral infusion of R848 for 25 h using a micropump to achieve durable therapeutic effects while minimizing the proinflammatory cytokine levels in the plasma post leakage of the drug into the circulation.</p><p><strong>Results: </strong>The results showed that prolonged immunotherapy with R848 (as low as 1 μg) significantly suppressed tumor growth (inhibition rates up to 98%, <i>p</i> < 0.01) in treated mice compared to control mice receiving regular intratumoral injection of R848. Higher levels of CD86⁺or CD11c⁺ D.C.s, CD4⁺/CD8⁺/OX40⁺ T cells, and cytokines (TNF-α/IFN-γ) were observed in the tumors and spleens of the mice in the treated group compared to the sham group (<i>p</i> < 0.05), indicating efficient activation of local and abscopal immunity by prolonged therapy with R848. Furthermore, the R848 functional concentration assay demonstrated that the micropump prolonged the treatment time of R848 drugs in tumors and reduced the requirement for higher doses, enhancing safety.</p><p><strong>Conclusion: </strong>Taken together, this study provides new insights into TLR7/8a immunotherapy for improved clinical performance, with potential benefits for patients with superficial tumors amenable to prolonged intratumoral infusion via micropump.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"27 1","pages":"2670801"},"PeriodicalIF":5.7,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13173998/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147926637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ABHD17C regulates the efficacy of lenvatinib in suppressing hepatocellular carcinoma.","authors":"Linpei Wang, Jiawei Wang, Xiaoqiu Ma, Jinfa Huang, Yingming Sun, Chunfeng Shi, Jiahui Zhang, Peng Li, Hao Xu, Hongtan Lin, Wei Wang","doi":"10.1080/15384047.2026.2693350","DOIUrl":"10.1080/15384047.2026.2693350","url":null,"abstract":"<p><strong>Introduction: </strong>Lenvatinib is a first-line therapy for hepatocellular carcinoma (HCC), but its clinical efficacy is limited by drug resistance. ABHD17C, a depalmitoylation enzyme involved in HCC progression, has not been investigated in lenvatinib response. This study aimed to determine whether ABHD17C regulates the anti-tumor efficacy of lenvatinib in HCC.</p><p><strong>Methods: </strong>Published single-cell RNA sequencing (scRNA-seq) data were analyzed to characterize ABHD17C expression in the HCC tumor microenvironment. Functional assays were performed in HCC cell lines to evaluate the effects of lenvatinib and ABHD17C modulation. The findings were validated using HCC xenograft mouse models and patient-derived tumor organoids.</p><p><strong>Results: </strong>scRNA-seq analysis showed that ABHD17C is associated with an immunosuppressive tumor microenvironment characterized by reduced CD8⁺ T cell infiltration, increased T cell exhaustion, and abnormal intercellular communication. In vitro, lenvatinib inhibited proliferation, migration, and invasion while inducing apoptosis and cell cycle arrest in HCC cells. These effects were significantly attenuated by ABHD17C overexpression but enhanced by ABHD17C depletion. In vivo, ABHD17C-overexpressing xenografts were less responsive to lenvatinib, exhibiting increased tumor growth and reduced apoptosis. Similarly, in patient-derived organoids, ABHD17C overexpression diminished lenvatinib efficacy. Notably, lenvatinib reduced ABHD17C expression in organoids, suggesting potential feedback regulation.</p><p><strong>Conclusion: </strong>ABHD17C promotes an immunosuppressive tumor microenvironment and attenuates the anti-tumor effects of lenvatinib in HCC. Targeting ABHD17C may represent a potential strategy to enhance lenvatinib sensitivity and improve therapeutic outcomes.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"27 1","pages":"2693350"},"PeriodicalIF":5.7,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13313231/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148326898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative single-cell and spatial transcriptomic approaches to decipher the tumor microenvironment and therapeutic resistance in pancreatic cancer.","authors":"Mengting Luo, Feng Shen, Wanli Xu, Christopher Corpe, Jin Wang","doi":"10.1080/15384047.2026.2699508","DOIUrl":"10.1080/15384047.2026.2699508","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) is among the most aggressive human malignancies and has an extremely poor prognosis. Its progression is largely driven by a highly complex and immunosuppressive tumor microenvironment (TME), highlighting the urgent need for a deeper understanding of its molecular mechanisms. Recent advances in single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) have provided unprecedented opportunities to dissect cellular heterogeneity, spatial organization, and gene expression dynamics within the TME. In this review, we summarize the major scRNA-seq and ST technologies and their unique strengths in cancer research and highlight their integrated applications in revealing PDAC heterogeneity, stromal-immune interactions, and mechanisms of therapeutic resistance. We further discuss how these approaches can inform biomarker discovery and guide the development of novel therapeutic strategies. Together, these findings suggest that integrated single-cell and spatial transcriptomics offers transformative potential to advance precision oncology and improve outcomes for patients with pancreatic cancer.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"27 1","pages":"2699508"},"PeriodicalIF":5.7,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13348943/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148395824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting molecular and genetic pathways driving tumorigenesis for precision therapy in colorectal cancer.","authors":"Allison S Doermann, Adi Caspi, Andrew E Evans, Andrea Feci, Ariana A Entezari, Adam E Snook, Scott A Waldman","doi":"10.1080/15384047.2026.2683096","DOIUrl":"10.1080/15384047.2026.2683096","url":null,"abstract":"<p><p>Colorectal cancer (CRC) remains a major global health challenge and a leading cause of cancer-related mortality worldwide. Central to its pathogenesis is the dysregulation of interconnected signal transduction networks that govern cellular proliferation, survival, differentiation, apoptosis, and immune modulation. Progressive disruption of these pathways facilitates malignant transformation of the colonic epithelium and underlies disease initiation and progression. In this review, we examine the foundational signaling mechanisms implicated in CRC, with an emphasis on the Wnt/β-catenin, GUCY2C, MAPK/ERK, p53, PI3K/AKT, and SMAD4/TGF-<i>β</i> pathways. We also highlight the genomic and epigenomic hallmarks of CRC to illustrate how genetic and epigenetic alterations contribute to diverse oncogenic processes. Furthermore, we discuss both conventional and emerging precision-based therapeutic strategies aimed at driving mutations in CRC tumorigenesis. By synthesizing advances in signaling biology, this review aims to provide a framework for understanding CRC complexity and to inform the development of more precise and effective therapies.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"27 1","pages":"2683096"},"PeriodicalIF":5.7,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13418715/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148590437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effective treatment of human breast tumors by chimeric CCL2 and CCL8 diphtheria toxin cytotoxic peptides.","authors":"Bernardo Chavez, Vitali Sikirzhytski, Chang-Uk Lim, Ioulia Chatzistamou, Hippokratis Kiaris","doi":"10.1080/15384047.2026.2688479","DOIUrl":"10.1080/15384047.2026.2688479","url":null,"abstract":"<p><strong>Objective: </strong>Chemokine receptors play crucial roles in tumor onset and progression, but the high redundancy between ligands and their receptors limits the possibilities to leverage them therapeutically for cancer management. To overcome this limitation, we developed chimeric chemokine peptides in which CCL2 and CCL8 were conjugated to diphtheria toxin (DT) and evaluated their antitumor activity.</p><p><strong>Methods: </strong>Cytotoxic peptides DTCCL2 and DTCCL8 were produced as recombinant proteins, and their anticancer activity was tested <i>in vitro</i> in cultured cells and <i>in vivo</i> in tumor-bearing mice. The uptake of the cytotoxic analogs was evaluated before and after therapy in tumor explants <i>ex vivo</i>.</p><p><strong>Results: </strong>Both analogs were cytotoxic to breast cancer cells in vitro and produced significant anticancer activity in vivo in mice bearing human breast cancer lines and hormone-negative breast cancer patient-derived xenografts (PDXs). In vitro, the peptide conjugates exhibited overlapping uptake profiles, with about 80% of the breast cancer cells being positive for both peptides and about 15%-20% of the cells being negative for either or both of the cytotoxic peptides. In tumor explants cultured ex vivo, simultaneous positivity for DTCCL2 and DTCCL8 increased to >95%, with less than 5% of the cells showing neither DTCCL8 nor DTCCL2 uptake. Treatment of breast cancer-bearing mice with DTCCL8 or DTCCL2 significantly inhibited tumor growth and prolonged survival in the PDX model.</p><p><strong>Conclusion: </strong>These results support the feasibility of cytotoxic peptide conjugates for breast cancer management and show that receptor expression profiles in vitro do not accurately forecast tumoral positivity.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"27 1","pages":"2688479"},"PeriodicalIF":5.7,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13336256/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148367221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fibroblast-associated TPM2 links cell-matrix remodeling to EMT-Notch signaling and gemcitabine resistance in intrahepatic cholangiocarcinoma.","authors":"Yingjiao Zhu, Zhibin Qiao, Zhuhong Chen, Yahua Wu, Lirong Xiao, Fangyu Lin, Xiaoyan Lin, Xinli Wang","doi":"10.1080/15384047.2026.2725344","DOIUrl":"10.1080/15384047.2026.2725344","url":null,"abstract":"<p><strong>Background: </strong>Intrahepatic cholangiocarcinoma (ICC) is an aggressive liver malignancy with heterogeneous responses to gemcitabine-based chemotherapy. The cellular and microenvironmental programs associated with the gemcitabine response remain incompletely understood. This study aimed to identify tumor microenvironment-associated regulators of gemcitabine response in ICC and evaluate their functional relevance using patient-derived organoids.</p><p><strong>Methods: </strong>Four public single-cell RNA sequencing datasets comprising 50,176 cells were integrated with TCGA-based transcriptomic and drug sensitivity analyses. High-dimensional weighted gene co-expression network analysis was used to identify cell type-associated modules. Predicted gemcitabine IC50-related differentially expressed genes were intersected with the fibroblast-associated module genes. Patient-derived ICC organoids were used for gemcitabine sensitivity testing and CRISPR/Cas9-mediated TPM2 knockout validation.</p><p><strong>Results: </strong>Single-cell analysis revealed fibroblast enrichment in ICC, and co-expression analysis identified fibroblast-associated modules enriched in extracellular matrix organization and ECM-receptor interaction. Integrated analysis identified TPM2 as a fibroblast-enriched candidate associated with poor prognosis, activation of epithelial-mesenchymal transition, TGF-<i>β</i> and Notch-related pathways, and dynamic cellular state transitions. Patient-derived ICC organoids retained features of matched tumors and showed distinct gemcitabine sensitivities that were broadly consistent with the clinical imaging responses. In a relatively gemcitabine-resistant organoid model, TPM2 knockout enhanced gemcitabine-induced cytotoxicity and suppressed EMT/ECM-related programs and Notch signaling.</p><p><strong>Conclusions: </strong>These findings identify TPM2-associated cell-matrix remodeling as a potential contributor to gemcitabine resistance in ICC and support patient-derived organoids as a functional platform for studying therapeutic vulnerabilities.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"27 1","pages":"2725344"},"PeriodicalIF":5.7,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13596889/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IGF2BP3 promotes gastric cancer progression by inhibiting ferroptosis through ETV4-mediated regulation of GCH1.","authors":"Kan Li, Hui Wei, Fang Li, Ya Zheng, Yongning Zhou","doi":"10.1080/15384047.2026.2664967","DOIUrl":"10.1080/15384047.2026.2664967","url":null,"abstract":"<p><strong>Background: </strong>Ferroptosis can be inhibited by insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) in cancers. ETS variant transcription factor 4 (ETV4) is aberrantly expressed in various cancers. Elevated transcription of guanosine triphosphate cyclohydrolase 1 (GCH1) contributes to tumor malignancy. This study investigated the involvement of IGF2BP3, ETV4, and GCH1 in ferroptosis in gastric cancer (GC).</p><p><strong>Methods: </strong>GC cells and tissue samples were used to detect IGF2BP3, ETV4, and GCH1 expression. The relationships between IGF2BP3, ETV4, and GCH1 were assessed using RNA immunoprecipitation assay, chromatin immunoprecipitation assay, and dual-luciferase reporter assay. BALB/c nude mice were utilized to establish GC tumor xenografts. Cell cloning and Transwell were used to detect the proliferation, migration, and invasion of cells.</p><p><strong>Results: </strong>IGF2BP3 and ETV4 were upregulated in GC. IGF2BP3 regulated ETV4 protein level by mediating its mRNA stability. Knockdown of ETV4 inhibited GC cell proliferation, migration, and invasion, and promoted their ferroptosis. ETV4 also promoted the transcription of GCH1 by directly binding to its promoter region. GCH1 overexpression diminished the facilitating effect of ETV4 knockdown on ferroptosis in GC. Overexpression of GCH1 also eliminated the promoting impact of IGF2BP3 knockdown on GC cell proliferation, migration, and invasion. Lastly, inhibition of GCH1 reversed the promoting effect of IGF2BP3 overexpression on GC tumor growth <i>in vivo</i>.</p><p><strong>Conclusions: </strong>IGF2BP3 promotes tumor growth and inhibits ferroptosis in GC by regulating ETV4, while ETV4 promotes GCH1 expression by direct interaction with its promoter. GCH1 overexpression counteracts the effects of ETV4 and IGF2BP3 on GC.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"27 1","pages":"2664967"},"PeriodicalIF":5.7,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13138077/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Downregulation of the lncRNA PGM5P4-AS1 predicts poor prognosis and drives breast cancer progression through miR-3664-5p/KLF9.","authors":"Yifan Wu, Jiangdong Jin, Yuhan Zhang, Xiaoya Huang, Hanjia Wang, Yue Huang, Hui Xie","doi":"10.1080/15384047.2025.2606474","DOIUrl":"10.1080/15384047.2025.2606474","url":null,"abstract":"<p><strong>Background: </strong>Accumulating evidence suggests that deregulated long non-coding RNAs (lncRNAs) drive breast cancer (BRCA) progression. This study investigated the expression profile and mechanism of PGM5P4 antisense RNA 1 (PGM5P4-AS1) in BRCA.</p><p><strong>Materials: </strong>The differentially expressed lncRNAs in BRCA were identified using the GEO dataset. Cancer and adjacent tissues were obtained from BRCA patients. Real-time quantitative polymerase chain reaction was used to quantify the expression of PGM5P4-AS1, microRNA (miR)-3664-5p, and Krüppel-like factor 9 (KLF9). The Chi-squared test was used to assess the clinicopathological correlation of PGM5P4-AS1. Kaplan-Meier curves and Cox regression were used to evaluate their prognostic significance. Cell Counting Kit-8 kits, flow cytometry, and Transwell assays were used to assess cell proliferation, migration, invasion, and apoptosis. Dual-luciferase reporter and RNA immunoprecipitation assays were used to analyze the gene-target interactions.</p><p><strong>Results: </strong>PGM5P4-AS1 downregulation in BRCA was consistently documented across three GEO datasets. In BRCA cancer tissues, both PGM5P4-AS1 and KLF9 were significantly downregulated, whereas miR-3664-5p was noticeably upregulated. A reduction in PGM5P4-AS1 was associated with tumor differentiation, tumor node metastasis staging, and lymph node metastasis. Low PGM5P4-AS1 expression independently predicts poor survival. Further, miR-3664-5p noticeably reverses the suppression of cell proliferation, migration, and invasion, as well as the promotion of apoptosis, induced by PGM5P4-AS1 overexpression. Mechanistically, miR-3664-5p targets PGM5P4-AS1/KLF9 directly, and KLF9 silencing reverses the cellular function inhibition caused by miR-3664-5p downregulation.</p><p><strong>Conclusion: </strong>This study first shows that decreased PGM5P4-AS1 in BRCA patients links to poor prognosis, promotes malignancy via miR-3664-5p/KLF9 axis, offering new therapy and prognosis in sight.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"27 1","pages":"2606474"},"PeriodicalIF":4.6,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12758259/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145846228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retinol dehydrogenase 11 promotes prostate cancer progression through upregulation of tropomyosin receptor kinase A.","authors":"Shenghan Wang, Shuyu Zhang, Zekun Xin, Zhentao Lei, Jie Xiong, Yuqiang Shi, Lin Yang, Qiang Gao, Kai Le, Bao Zhang","doi":"10.1080/15384047.2026.2682051","DOIUrl":"https://doi.org/10.1080/15384047.2026.2682051","url":null,"abstract":"<p><strong>Objective: </strong>To clarify the clinical significance and biological function of retinol dehydrogenase-11 (RDH11) in prostate cancer (PCa) and to elucidate the downstream signaling mechanism through which it drives tumor progression.</p><p><strong>Methods: </strong>Public and in-house transcriptomic data were mined to compare RDH11 levels between PCa and matched normal tissues. RDH11 was stably silenced (shRDH11) or over-expressed (oeRDH11) in PC-3, DU145, and LNCaP cells; cell proliferation, migration, and invasion were quantified with CCK-8 and Transwell assays. RNA-seq and gene set enrichment analysis (GSEA) were performed to screen downstream targets and pathways. Rescue experiments in vitro and in vivo were used to confirm the mechanism.</p><p><strong>Results: </strong>RDH11 levels were markedly elevated in human PCa tissues and cell lines. Silencing RDH11 hindered PCa cell proliferation, migration, and invasion, whereas its overexpression had the opposite effects. Mechanistically, we identified the tropomyosin receptor kinase (TRKA) and STAT3 signaling pathway as the downstream gene and pathway of RDH11. Rescue assays using PC3, DU145, and LNCaP cells demonstrated that RDH11 facilitated PCa progression by upregulation of TRKA and the activation of STAT3 signaling. <i>In vivo</i> studies further confirmed that RDH11 overexpression enhanced prostate tumor growth, whereas TRKA knockdown counteracted the oncogenic effects of RDH11.</p><p><strong>Conclusion: </strong>RDH11 promotes the development of PCa through the upregulation of TRKA and activation of the STAT3 signaling pathway.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"27 1","pages":"2682051"},"PeriodicalIF":5.7,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148263595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of leucine-rich diet on placenta's proteomic and metabolomic profiles of pregnant tumor-bearing rats.","authors":"Igor Fernando Dos Santos, Carla de Moraes Salgado, Victor Corasolla Carregari, Rogerio Williams Dos Santos, Daniel Martins de Souza, Laís Rosa Viana, Maria Cristina Cintra Gomes-Marcondes","doi":"10.1080/15384047.2026.2670792","DOIUrl":"10.1080/15384047.2026.2670792","url":null,"abstract":"<p><strong>Background: </strong>Cancer during pregnancy is a fragile scenario where the maternal body undergoes significant molecular changes, including at proteomic and metabolomic levels, with damage to placenta and fetal development. Proteomic and metabolomic interaction analyses can clarify the complex dynamics in cancer associated with pregnancy. Leucine is involved in protein synthesis and metabolic regulation and may attenuate tumor-induced damage.</p><p><strong>Objective: </strong>We investigated placental proteomic and metabolomic profiles in the complex relationships among pregnancy, cancer, and leucine supplementation.</p><p><strong>Materials: </strong>Exploratory, non-targeted proteomic (mass spectrometry) and metabolomic (NMR spectrometry) analyses were performed on the placenta tissue of four pregnant groups: control (PC), Walker-256 tumor-bearing (PW), leucine (PL), and tumor-bearing fed a leucine-rich diet (PWL). Statistical comparisons were performed on technical replicate data within each group.</p><p><strong>Results: </strong>Tumor affected maternal weight, but leucine attenuated the decrease in placental weight and fetal resorption. Leucine supplementation restored the placental proteins involved in the nuclear structure, cytoskeleton, and immune response. Tumor evolution impaired pathways related to protein folding and chromosome localization, whereas leucine modulated interferon-gamma and hydrogen peroxide responses. PW placentas exhibited decreased adenosine, glucose, glutamate, and succinate, with enhanced lactate, creatine, and histamine levels, whereas leucine supplementation restored adenosine and pyridoxine and reduced lactate levels. The affected alanine/aspartate/glutamate and purine metabolism, beta-alanine metabolism, and the citrate cycle were minimized in leucine treatment (PWL), which mainly modulates purine and alanine/aspartate/glutamate pathways and pyruvate metabolism.</p><p><strong>Conclusion: </strong>A leucine-rich diet partially restored placental protein and metabolite levels, leading affected pathways to shift towards amino acid biosynthesis and pyruvate metabolism and minimizing effects on fetal development.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"27 1","pages":"2670792"},"PeriodicalIF":5.7,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13182973/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147940351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}