Molecular Cancer最新文献

{"title":"Immunomodulatory gene networks predict treatment response and survival to de-escalated, anthracycline-free neoadjuvant chemotherapy in triple-negative breast cancer in the WSG-ADAPT-TN trial","authors":"Darren Korbie, Clare Stirzaker, Oleg Gluz, Christine zu Eulenburg, Ulrike Nitz, Matthias Christgen, Sherko Kuemmel, Eva-Maria Grischke, Helmut Forstbauer, Michael Braun, Mathias Warm, John Hackmann, Christoph Uleer, Bahriye Aktas, Claudia Schumacher, Rachel Wuerstlein, Enrico Pelz, Hans Heinrich Kreipe, Susan J. Clark, Matt Trau, Monika Graeser, Nadia Harbeck","doi":"10.1186/s12943-025-02275-0","DOIUrl":"https://doi.org/10.1186/s12943-025-02275-0","url":null,"abstract":"Anthracycline-containing neoadjuvant chemotherapy (NACT) is the standard treatment for early triple-negative breast cancer (eTNBC); however, it is associated with substantial toxicity. We performed whole transcriptome profiling of baseline tumor biopsies to identify gene networks predictive and prognostic for pathological complete response (pCR) and survival after de-escalated, anthracycline-free NACT in the WSG-ADAPT-TN trial (NCT01815242). eTNBC patients (cT1c-cT4c, cN +) were randomized to 12 weeks of nab-paclitaxel + gemcitabine (n = 182) or nab-paclitaxel + carboplatin (n = 154). The primary endpoint was pCR (ypT0/is, ypN0), and the secondary endpoints included survival and translational research. AmpliSeq RNA sequencing, allowing simultaneous analysis of the expression of > 20,000 genes, was performed in 135 patients. Differentially expressed genes were evaluated in training (n = 67) and validation (n = 68) sets, and a polygenic score (PS) for prediction of pCR (PS:pCR) and a PS for prediction of invasive disease-free survival (PS:iDFS) were found. 49/135 (36.3%) patients had pCR; 30 iDFS events occurred during 60-month median follow-up. Immune recruitment and viral defense gene networks were strongly associated with pCR, while metabolic pathways were associated with survival. PS:pCR and PS:iDFS predominantly included immune-related genes. Diagnostic accuracy (ROC AUC) in the validation cohort was 83% for PS:pCR and 64% for PS:iDFS. At optimized cut-off, PS:pCR identified a group with a 67.7% pCR rate (vs. 10.8%; p < .0001), and PS:iDFS detected a group with 79.5% (95%CI 64.1%, 88.8%) 5-year iDFS rate (vs. 55.0%, 95%CI 29.8%, 74.5%; p = .04). Polygenic scores incorporating immunoregulatory genes can predict pCR and survival and represent an opportunity to select patients for de-escalated, anthracycline-free NACT. This transcriptome network analysis also identifies potential new targets for personalized medicine approaches in patients without response to NACT. NCT01815242.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"28 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143702980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of 6-phosphogluconate dehydrogenase suppresses esophageal squamous cell carcinoma growth and enhances the anti-tumor effects of metformin via the AMPK/mTOR pathway","authors":"Bei Wang, Zixuan Wang, Zini Zhou, Gui Liu, Zhenyuan Jiang, Mingyue Zheng, Wei Geng","doi":"10.1186/s12943-025-02302-0","DOIUrl":"https://doi.org/10.1186/s12943-025-02302-0","url":null,"abstract":"Metabolic reprogramming plays a pivotal role in the development and progression of tumors. Tumor cells rely on glycolysis as their primary energy production pathway and effectively utilize biomolecules generated by the pentose phosphate pathway (PPP) for efficient biosynthesis. However, the role of 6-phosphogluconate dehydrogenase (6PGD), a crucial enzyme in the PPP, remains unexplored in esophageal squamous cell carcinoma (ESCC). In this study, we observed a significant upregulation of 6PGD expression in ESCC tissues, which correlated with an unfavorable prognosis among patients. The experiments demonstrated that knockdown of 6PGD induces oxidative stress and suppresses ESCC cell proliferation. Mechanistically, this is achieved through AMPK activation and subsequent inhibition of downstream mTOR phosphorylation. Moreover, physcion has been found to inhibit 6PGD activity and exert its anti-ESCC effect via the AMPK/mTOR pathway. Subsequently, we conducted both in vitro and in vivo experiments to validate the anticancer efficacy of combining metformin, an AMPK activator, with physcion. The results demonstrated a significantly enhanced inhibition of ESCC growth. This study elucidates the impact of 6PGD on ESCC cell proliferation along with its underlying molecular mechanisms, highlighting its potential as a therapeutic target for ESCC. Furthermore, we investigated a novel approach for improved anti-tumor therapy involving physcion and metformin. These findings will contribute new insights to clinical treatment strategies for ESCC while providing a theoretical foundation for developing molecular targeted therapies.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"14 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143702979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circular RNA circDCUN1D4 suppresses hepatocellular carcinoma development via targeting the miR-590-5p/ TIMP3 axis","authors":"Hongyu Li, Bing Su, Yan Jiang, Boyang Zhang, Rulong Du, Can Song, Bin Hou, Kun Xu, Lida Wu, Yuchun Gu","doi":"10.1186/s12943-025-02300-2","DOIUrl":"https://doi.org/10.1186/s12943-025-02300-2","url":null,"abstract":"Hepatocellular carcinoma (HCC) is a major global health concern, necessitating innovative therapeutic strategies. In this study, we investigated the functional role of circular RNA circDCUN1D4 in HCC progression and its potential therapeutic implications. It was found that HCC patients exhibiting higher levels of circDCUN1D4 demonstrated a more favorable survival rate. Furthermore, we revealed that circDCUN1D4 suppressed HCC cell proliferation, migration, and invasion. Mechanistically, circDCUN1D4 was identified as a sponge for miR-590-5p, leading to the downregulation of its downstream target, Tissue Inhibitor of Metalloproteinase 3 (TIMP3). Importantly, circDCUN1D4 administration through In vivo jet-PEI exhibited a robust inhibitory effect on tumor progression without causing notable toxicity in mice. Overall, our findings highlight circDCUN1D4 as a promising therapeutic candidate for HCC, unraveling its intricate regulatory role through the miR-590-5p/TIMP3 axis. This study contributes valuable insights into the potential clinical applications of circRNA-based therapies for HCC.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"14 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143695089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EGFR-mediated local invasiveness and response to Cetuximab in head and neck cancer","authors":"Jiefu Zhou, Min He, Qiong Zhao, Enxian Shi, Hairong Wang, Vaidehi Ponkshe, Jiahang Song, Zhengquan Wu, Dongmei Ji, Gisela Kranz, Anna Tscherne, Sabina Schwenk-Zieger, Nilofer Abdul Razak, Julia Hess, Claus Belka, Horst Zitzelsberger, Iordanis Ourailidis, Fabian Stögbauer, Melanie Boxberg, Jan Budczies, Christoph A. Reichel, Martin Canis, Philipp Baumeister, Hongxia Wang, Kristian Unger, Andreas Mock, Olivier Gires","doi":"10.1186/s12943-025-02290-1","DOIUrl":"https://doi.org/10.1186/s12943-025-02290-1","url":null,"abstract":"Recurrent/metastatic head and neck squamous cell carcinoma (R/M-HNSCC) is a severe, frequently lethal condition. Oncogene addiction to epidermal growth factor receptor (EGFR) is a hallmark of HNSCC, but the clinical efficacy of EGFR-targeted therapies remains low. Understanding molecular networks governing EGFR-driven progression is paramount to the exploration of (co)-treatment targets and predictive markers. We performed function-based mapping of differentially expressed genes in EGFR-mediated local invasion (fDEGs) using photoconvertible tracers and RNA-sequencing (RNA-seq) in a cellular 3D-model. Upon alignment with public single-cell RNA-seq (scRNA-seq) datasets and HNSCC-specific regulons, a gene regulatory network of local invasion (invGRN) was inferred from gene expression data, which was overrepresented in budding tumors. InvGRN comprises the central hubs inhibin subunit beta alpha (INHBA) and snail family transcriptional repressor 2 (SNAI2), and druggable fDEGs integrin subunit beta 4 (ITGB4), laminin 5 (LAMB3/LAMC2), and sphingosine kinase 1 (SPHK1). Blockade of INHBA repressed local invasion and was reverted by activin A, laminin 5, and sphingosine-1-phosphate, demonstrating a functional interconnectivity of the invGRN. Epithelial-to-mesenchymal transition (EMT) of malignant cells and the invGRN are induced by newly defined EGFR-activity subtypes with prognostic value that are promoted by amphiregulin (AREG) and epiregulin (EREG). Importantly, co-inhibition of SPHK1 showed synthetic effects on Cetuximab-mediated invasion blockade and high expression of selected fDEGs was associated with response to Cetuximab in patient-derived xenotransplantation (PDX) and R/M-HNSCC patients. We describe an actionable network of EGFR-mediated local invasion and define druggable effectors with predictive potential regarding the response of R/M-HNSCC to Cetuximab.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"61 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143672269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: The circROBO1/KLF5/FUS feedback loop regulates the liver metastasis of breast cancer by inhibiting the selective autophagy of afadin","authors":"Zehao Wang, Lu Yang, Peng Wu, Xing Li, Yuhui Tang, Xueqi Ou, Yue Zhang, Xiangsheng Xiao, Jin Wang, Hailin Tang","doi":"10.1186/s12943-025-02296-9","DOIUrl":"https://doi.org/10.1186/s12943-025-02296-9","url":null,"abstract":"&lt;p&gt;&lt;b&gt;Correction&lt;/b&gt;&lt;b&gt;: &lt;/b&gt;&lt;b&gt;Mol Cancer 21, 29 (2022)&lt;/b&gt;&lt;/p&gt;&lt;p&gt;&lt;b&gt;https://doi.org/10.1186/s12943-022–01498-9&lt;/b&gt;&lt;/p&gt;&lt;br/&gt;&lt;p&gt;Following the publication of the original article [1], the authors reported that there were three mistakes in the publication version. The three mistakes are, (1) in Figure 2C, the si-circROBO1 group of the BT-549 cell line was mistakenly repeated with the Vector group and (2) in Figure 5L, the circROBO1+mimics-NC 0h group of the MCF-7 cell line was unintentionally repeated with the Vector 0h group from Figure 2F. (3) in Additional File Table S1, the sequence of si-circROBO1-1 and si-circROBO1-2 were copied by mistake. To ensure its accuracy, we wish to correct these errors by replacing correct images in Figure 2C, Figure 5L and Additional File Table S1. The corrections do not alter the findings and conclusions of the study. The incorrect and correct Figures 2 and 5, as well as the correct Additional file 1, are provided below.&lt;/p&gt;&lt;p&gt;Incorrect Figures 2 and 5:&lt;/p&gt;&lt;figure&gt;&lt;picture&gt;&lt;source srcset=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-025-02296-9/MediaObjects/12943_2025_2296_Figa_HTML.png?as=webp\" type=\"image/webp\"/&gt;&lt;img alt=\"figure a\" aria-describedby=\"Figa\" height=\"974\" loading=\"lazy\" src=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-025-02296-9/MediaObjects/12943_2025_2296_Figa_HTML.png\" width=\"685\"/&gt;&lt;/picture&gt;&lt;/figure&gt;&lt;figure&gt;&lt;picture&gt;&lt;source srcset=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-025-02296-9/MediaObjects/12943_2025_2296_Figb_HTML.png?as=webp\" type=\"image/webp\"/&gt;&lt;img alt=\"figure b\" aria-describedby=\"Figb\" height=\"982\" loading=\"lazy\" src=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-025-02296-9/MediaObjects/12943_2025_2296_Figb_HTML.png\" width=\"685\"/&gt;&lt;/picture&gt;&lt;/figure&gt;&lt;p&gt;Correct Figures 2 and 5:&lt;/p&gt;&lt;figure&gt;&lt;picture&gt;&lt;source srcset=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-025-02296-9/MediaObjects/12943_2025_2296_Figc_HTML.png?as=webp\" type=\"image/webp\"/&gt;&lt;img alt=\"figure c\" aria-describedby=\"Figc\" height=\"973\" loading=\"lazy\" src=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-025-02296-9/MediaObjects/12943_2025_2296_Figc_HTML.png\" width=\"685\"/&gt;&lt;/picture&gt;&lt;/figure&gt;&lt;figure&gt;&lt;picture&gt;&lt;source srcset=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-025-02296-9/MediaObjects/12943_2025_2296_Figd_HTML.png?as=webp\" type=\"image/webp\"/&gt;&lt;img alt=\"figure d\" aria-describedby=\"Figd\" height=\"982\" loading=\"lazy\" src=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-025-02296-9/MediaObjects/12943_2025_2296_Figd_HTML.png\" width=\"685\"/&gt;&lt;/picture&gt;&lt;/figure&gt;&lt;ol data-track-component=\"outbound reference\" data-track-context=\"references section\"&gt;&lt;li data-counter=\"1.\"&gt;&lt;p&gt;Wang Z, Yang L, Wu P, et al. The circROBO1/KLF5/FUS feedback loop regulates the liver metastasis of breast","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"32 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143665936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Sorafenib enhanced the function of myeloid‑derived suppressor cells in hepatocellular carcinoma by facilitating PPARα‑mediated fatty acid oxidation","authors":"Chunxiao Li, Liting Xiong, Yuhan Yang, Ping Jiang, Junjie Wang, Mengyuan Li, Shuhua Wei, Suqing Tian, Yuexuan Wang, Mi Zhang, Jie Tang","doi":"10.1186/s12943-025-02303-z","DOIUrl":"https://doi.org/10.1186/s12943-025-02303-z","url":null,"abstract":"&lt;p&gt;&lt;b&gt;Correction&lt;/b&gt;&lt;b&gt;: &lt;/b&gt;&lt;b&gt;Mol Cancer 24, 34 (2025)&lt;/b&gt;&lt;/p&gt;&lt;p&gt;&lt;b&gt;https://doi.org/10.1186/s12943-025–02238-5&lt;/b&gt;&lt;/p&gt;&lt;br/&gt;&lt;p&gt;Following publication of the original article [1], the author has requested the publication of an erratum to address the following issues stated below.&lt;/p&gt;&lt;p&gt;Figure 9B-9E. The authors believe that in the original article, the analysis of MDSCs (myeloid-derived suppressor cells) was conducted based on the CD45.1 and CD45.2 markers, where CD45.1 represents &lt;i&gt;Ppara&lt;/i&gt;&lt;sup&gt;+/+&lt;/sup&gt; WT and CD45.2 represents &lt;i&gt;Ppara&lt;/i&gt;&lt;sup&gt;-/-&lt;/sup&gt; KO. However, in the original article, the author only labeled &lt;i&gt;Ppara&lt;/i&gt;&lt;sup&gt;+/+&lt;/sup&gt; and &lt;i&gt;Ppara&lt;/i&gt;&lt;sup&gt;-/-&lt;/sup&gt; above the figure. This labeling method could potentially lead to misunderstandings, making readers mistakenly believe that these two experimental groups were derived from two independent mouse models, rather than a mixed chimeric model of the same recipient. To enhance the clarity of data analysis and avoid unnecessary misunderstandings, the author reanalyzed the data and implemented the following improvements: First, by gating CD11B+GR1+TGFB+ MDSC cells to ensure the selection of a functionally relevant MDSC population; then, analyzing based on the ratio of CD45.1 and CD45.2 to more clearly compare the responses of MDSCs from different sources to Sorafenib treatment within the same tumor microenvironment. Importantly, this optimization did not alter the study's conclusions, and the trends in the results remained consistent.&lt;/p&gt;&lt;p&gt;New Figure 9B-9E:&lt;/p&gt;&lt;figure&gt;&lt;picture&gt;&lt;source srcset=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-025-02303-z/MediaObjects/12943_2025_2303_Figa_HTML.png?as=webp\" type=\"image/webp\"/&gt;&lt;img alt=\"figure a\" aria-describedby=\"Figa\" height=\"451\" loading=\"lazy\" src=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-025-02303-z/MediaObjects/12943_2025_2303_Figa_HTML.png\" width=\"685\"/&gt;&lt;/picture&gt;&lt;/figure&gt;&lt;ol data-track-component=\"outbound reference\" data-track-context=\"references section\"&gt;&lt;li data-counter=\"1.\"&gt;&lt;p&gt;Li C, Xiong L, Yang Y, et al. Sorafenib enhanced the function of myeloid-derived suppressor cells in hepatocellular carcinoma by facilitating PPARα-mediated fatty acid oxidation. Mol Cancer. 2025;24:34. https://doi.org/10.1186/s12943-025-02238-5.&lt;/p&gt;&lt;p&gt;Article CAS PubMed PubMed Central Google Scholar &lt;/p&gt;&lt;/li&gt;&lt;/ol&gt;&lt;p&gt;Download references&lt;svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"&gt;&lt;use xlink:href=\"#icon-eds-i-download-medium\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"&gt;&lt;/use&gt;&lt;/svg&gt;&lt;/p&gt;&lt;span&gt;Author notes&lt;/span&gt;&lt;ol&gt;&lt;li&gt;&lt;p&gt;Chunxiao Li, Liting Xiong and Yuhan Yang contributed equally to this work.&lt;/p&gt;&lt;/li&gt;&lt;/ol&gt;&lt;h3&gt;Authors and Affiliations&lt;/h3&gt;&lt;ol&gt;&lt;li&gt;&lt;p&gt;Department of Radiation Oncology, Peking University Third Hospital, Beijing, 100191, China&lt;/p&gt;&lt;p&gt;Chunxiao Li, Liting Xiong, Yuhan Yang, Ping Jiang, Junjie Wang, Mengyuan Li, Shuhua Wei, Suqing Tian, Yuexuan Wang, Mi Z","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"27 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143665862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3D tumor cultures for drug resistance and screening development in clinical applications","authors":"Zheng Peng, Xiaolan Lv, Hao Sun, Lina Zhao, Shigao Huang","doi":"10.1186/s12943-025-02281-2","DOIUrl":"https://doi.org/10.1186/s12943-025-02281-2","url":null,"abstract":"Tumor drug resistance presents a growing challenge in medical practice, particularly during anti-cancer therapies, where the emergence of drug-resistant cancer cells significantly complicates clinical treatment. In recent years, three-dimensional (3D) tumor culture technology, which more effectively simulates the in vivo physiological environment, has gained increasing attention in tumor drug resistance research and clinical applications. By mimicking the in vivo cellular microenvironment, 3D tumor culture technology not only recapitulates cell-cell interactions but also more faithfully reproduces the biological effects of therapeutic agents. Consequently, 3D tumor culture technology is emerging as a crucial tool in biomedical and clinical research. We summarize the benefits of 3D culture models and organoid technology, explore their application in the realm of drug resistance, drug screening, and personalized therapy, and discuss their potential application prospects and challenges in clinical transformation, with the aim of providing insights for optimizing cancer treatment strategies and advancing precision therapy.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"21 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143665861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding gold nanoparticles and their attributes in ovarian cancer therapy","authors":"Rishabh Aggarwal, Afsana Sheikh, Masheera Akhtar, Mohammed Ghazwani, Umme Hani, Amirhossein Sahebkar, Prashant Kesharwani","doi":"10.1186/s12943-025-02280-3","DOIUrl":"https://doi.org/10.1186/s12943-025-02280-3","url":null,"abstract":"Ovarian cancer is one the deadliest disease wherein the survival rate is very low. Despite of advances in medical sciences, researches are still at the stage of infancy where patients are succumbing to this malignancy. Multidrug resistance, toxicity, mode of treatment related issues like catheter related complication poises a number of challenges to scientists worldwide. Novel therapy is now thus being focussed to sensitive the cells more towards the treatment. Gold nanoparticles (Au NPs), known for their high biocompatibility, and strong optical and magnetic responses, have emerged as promising agents for both the diagnosis and treatment of ovarian cancer. Owing to physical characteristics, AuNPs may be used as adjuvants in bioimaging, radiotherapy and fluorescence imaging. As a result, these characteristics substantially support AuNPs in biological domains. In addition to their therapeutic potential, Au NPs exhibit strong surface plasmon resonance (SPR) properties, enhancing imaging techniques for early detection of ovarian tumors. Furthermore, chemical properties such as Magnetic Resonance and Imaging Properties, X-ray imaging property, Two-photon or multiphoton imaging, and Optical coherence tomography (OCT) imaging properties enhance the use of Au NPs in diagnosis. This paper highlights the properties, targeting potential and diagnosis and treatment of ovarian cancer by Au NPs has been discussed. ","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"183 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143661318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual role of interferon-gamma in the response of melanoma patients to immunotherapy with immune checkpoint inhibitors","authors":"Piotr Wawrzyniak, Mariusz L. Hartman","doi":"10.1186/s12943-025-02294-x","DOIUrl":"https://doi.org/10.1186/s12943-025-02294-x","url":null,"abstract":"Interferon-gamma (IFN-γ) is a cytokine produced mainly by immune cells and can affect cancer cells by modulating the activity of multiple signaling pathways, including the canonical Janus-activated kinase/signal transducer and activator of transcription (JAK/STAT) cascade. In melanoma, IFN-γ can exert both anticancer effects associated with cell-cycle arrest and cell death induction and protumorigenic activity related to immune evasion leading to melanoma progression. Notably, IFN-γ plays a crucial role in the response of melanoma patients to immunotherapy with immune checkpoint inhibitors (ICIs), which are currently used in the clinic. As these agents target programmed death-1 (PD-1) and its ligand (PD-L1), cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) and lymphocyte-activation gene 3 (LAG-3), they are designed to restore the antimelanoma immune response. In this respect, IFN-γ produced by cells in the tumor microenvironment in response to ICIs has a beneficial influence on both immune and melanoma cells by increasing antigen presentation, recruiting additional T-cells to the tumor site, and inducing direct antiproliferative effects and apoptosis in melanoma cells. Therefore, IFN-γ itself and IFN-γ-related gene signatures during the response to ICIs can constitute biomarkers or predictors of the clinical outcome of melanoma patients treated with ICIs. However, owing to its multifaceted roles, IFN-γ can also contribute to developing mechanisms associated with the acquisition of resistance to ICIs. These mechanisms can be associated with either decreased IFN-γ levels in the tumor microenvironment or diminished responsiveness to IFN-γ due to changes in the melanoma phenotypes associated with affected activity of other signaling pathways or genetic alterations e.g., in JAK, which restricts the ability of melanoma cells to respond to IFN-γ. In this respect, the influence of IFN-γ on melanoma-specific regulators of the dynamic plasticity of the cell phenotype, including microphthalmia-associated transcription factor (MITF) and nerve growth factor receptor (NGFR)/CD271 can affect the clinical efficacy of ICIs. This review comprehensively discusses the role of IFN-γ in the response of melanoma patients to ICIs with respect to its positive influence and role in IFN-γ-related mechanisms of resistance to ICIs as well as the potential use of predictive markers on the basis of IFN-γ levels and signatures of IFN-γ-dependent genes.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"34 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143661313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA damage response signatures are associated with frontline chemotherapy response and routes of tumor evolution in extensive stage small cell lung cancer","authors":"Benjamin B. Morris, Simon Heeke, Yuanxin Xi, Lixia Diao, Qi Wang, Pedro Rocha, Edurne Arriola, Myung Chang Lee, Darren R. Tyson, Kyle Concannon, Kavya Ramkumar, C. Allison Stewart, Robert J. Cardnell, Runsheng Wang, Vito Quaranta, Jing Wang, John V. Heymach, Barzin Y. Nabet, David S. Shames, Carl M. Gay, Lauren A. Byers","doi":"10.1186/s12943-025-02291-0","DOIUrl":"https://doi.org/10.1186/s12943-025-02291-0","url":null,"abstract":"A hallmark of small cell lung cancer (SCLC) is its recalcitrance to therapy. While most SCLCs respond to frontline therapy, resistance inevitably develops. Identifying phenotypes potentiating chemoresistance and immune evasion is a crucial unmet need. Previous reports have linked upregulation of the DNA damage response (DDR) machinery to chemoresistance and immune evasion across cancers. However, it is unknown if SCLCs exhibit distinct DDR phenotypes. To study SCLC DDR phenotypes, we developed a new DDR gene analysis method and applied it to SCLC clinical samples, in vitro, and in vivo model systems. We then investigated how DDR regulation is associated with SCLC biology, chemotherapy response, and tumor evolution following therapy. Using multi-omic profiling, we demonstrate that SCLC tumors cluster into three DDR phenotypes with unique molecular features. Hallmarks of these DDR clusters include differential expression of DNA repair genes, increased replication stress, and heightened G2/M cell cycle arrest. SCLCs with elevated DDR phenotypes exhibit increased neuroendocrine features and decreased “inflamed” biomarkers, both within and across SCLC subtypes. Clinical analyses demonstrated treatment naive DDR status was associated with different responses to frontline chemotherapy. Using longitudinal liquid biopsies, we found that DDR Intermediate and High tumors exhibited subtype switching and coincident emergence of heterogenous phenotypes following frontline treatment. We establish that SCLC can be classified into one of three distinct, clinically relevant DDR clusters. Our data demonstrates that DDR status plays a key role in shaping SCLC phenotypes and may be associated with different chemotherapy responses and patterns of tumor evolution. Future work targeting DDR specific phenotypes will be instrumental in improving patient outcomes.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"11 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143661310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}