Molecular Cancer最新文献

{"title":"Membrane-bound IL-7 immobilized by the CD8 transmembrane region improves efficacy of CD19 CAR-T cell therapy","authors":"Chaoting Zhang, Ting Liu, Shance Li, Xia Teng, Yuge Zhu, Guanyu Zhang, Huimin Xie, Kang Sun, Jiaxin Tu, Wenjun Yang, Zheming Lu","doi":"10.1186/s12943-024-02154-0","DOIUrl":"https://doi.org/10.1186/s12943-024-02154-0","url":null,"abstract":"Enhancing the efficacy of CD19 CAR-T cell therapy can significantly improve patient outcomes by reducing relapse rates in CD19 + B cell malignancies. Exogenous or transgenic cytokines are often used to boost the expansion and durability of CAR-T cells but pose risks of severe toxicities. A promising approach to address these limitations is to immobilize cytokines on the surface of CAR-T cells using transmembrane (TM) anchor domains. Given IL-7 can enhance T-cell proliferation and antitumor activity, our study developed membrane-bound IL-7 constructs using different TM anchor domains (CD8, CD28 and B7-1). We primarily found that the CD8 TM provided superior anchoring for IL-7 compared to CD28 and B7-1. Moreover, the IL-7 construct with a CD8 TM (IL7/CD8) enhanced naïve T cell proliferation and effector functions, and improved the in vitro and in vivo antitumor activity of CD19 CAR-T cells. Importantly, although IL7/CD8 could promote T-cell proliferation, it did not sustain long-term autonomous expansion, which could ensure the safety of CD19 CAR-T cells expressing IL7/CD8 in clinical applications. Collectively, the IL7/CD8 construct represents a promising strategy for enhancing the therapeutic potential of CD19 CAR-T cell therapy.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"67 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142487528","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":"MicroRNAs are enriched at COVID-19 genomic risk regions, and their blood levels correlate with the COVID-19 prognosis of cancer patients infected by SARS-CoV-2","authors":"Simone Anfossi, Faezeh Darbaniyan, Joseph Quinlan, Steliana Calin, Masayoshi Shimizu, Meng Chen, Paola Rausseo, Michael Winters, Elena Bogatenkova, Kim-Anh Do, Ivan Martinez, Ziyi Li, Loredana Antal, Tudor Rares Olariu, Ignacio Wistuba, George A. Calin","doi":"10.1186/s12943-024-02094-9","DOIUrl":"https://doi.org/10.1186/s12943-024-02094-9","url":null,"abstract":"Cancer patients are more susceptible to an aggressive course of COVID-19. Developing biomarkers identifying cancer patients at high risk of COVID-19-related death could help determine who needs early clinical intervention. The miRNAs hosted in the genomic regions associated with the risk of aggressive COVID-19 could represent potential biomarkers for clinical outcomes. Plasma samples were collected at The University of Texas MD Anderson Cancer Center from cancer patients (N = 128) affected by COVID-19. Serum samples were collected from vaccinated healthy individuals (n = 23) at the Municipal Clinical Emergency Teaching Hospital in Timisoara, Romania. An in silico positional cloning approach was used to identify the presence of miRNAs at COVID-19 risk-associated genomic regions: CORSAIRs (COvid-19 RiSk AssocIated genomic Regions). The miRNA levels were measured by RT-qPCR. We found that miRNAs were enriched in CORSAIR. Low plasma levels of hsa-miR-150-5p and hsa-miR-93-5p were associated with higher COVID-19-related death. The levels of hsa-miR-92b-3p were associated with SARS-CoV-2 test positivity. Peripheral blood mononuclear cells (PBMC) increased secretion of hsa-miR-150-5p, hsa-miR-93-5p, and hsa-miR-92b-3p after in vitro TLR7/8- and T cell receptor (TCR)-mediated activation. Increased levels of these three miRNAs were measured in the serum samples of healthy individuals between one and nine months after the second dose of the Pfizer-BioNTech COVID-19 vaccine. SARS-CoV-2 infection of human airway epithelial cells influenced the miRNA levels inside their secreted extracellular vesicles. MiRNAs are enriched at CORSAIR. Plasma miRNA levels can represent a potential blood biomarker for predicting COVID-19-related death in cancer patients.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"20 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142452072","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":"Anti irradiation nanoparticles shelter immune organ from radio-damage via preventing the IKK/IκB/NF-κB activation","authors":"Shigao Huang, Min Xu, Xiaojun Deng, Qingyue Da, Miaomiao Li, Hao Huang, Lina Zhao, Linlin Jing, Haibo Wang","doi":"10.1186/s12943-024-02142-4","DOIUrl":"https://doi.org/10.1186/s12943-024-02142-4","url":null,"abstract":"Normal tissue and immune organ protection are critical parts of the tumor radiation therapy process. Radiation-induced immune organ damage (RIOD) causes several side reactions by increasing oxidative stress and inflammatory responses, resulting in unsatisfactory curability in tumor radiation therapy. The aim of this study was to develop a novel and efficient anti irradiation nanoparticle and explore its mechanism of protecting splenic tissue from radiation in mice. Nanoparticles of triphenylphosphine cation NIT radicals (NPs-TPP-NIT) were prepared and used to protect the spleens of mice irradiated with X-rays. Splenic tissue histopathology and hematological parameters were investigated to evaluate the protective effect of NPs-TPP-NIT against X-ray radiation. Proteomics was used to identify differentially expressed proteins related to inflammatory factor regulation. In addition, in vitro and in vivo experiments were performed to assess the impact of NPs-TPP-NIT on radiation therapy. NPs-TPP-NIT increased superoxide dismutase, catalase, and glutathione peroxidase activity and decreased malondialdehyde levels and reactive oxygen species generation in the spleens of mice after exposure to 6.0 Gy X-ray radiation. Moreover, NPs-TPP-NIT inhibited cell apoptosis, blocked the activation of cleaved cysteine aspartic acid–specific protease/proteinase, upregulated the expression of Bcl-2, and downregulated that of Bax. We confirmed that NPs-TPP-NIT prevented the IKK/IκB/NF-κB activation induced by ionizing radiation, thereby alleviating radiation-induced splenic inflammatory damage. In addition, when used during radiotherapy for tumors in mice, NPs-TPP-NIT exhibited no significant toxicity and conferred no significant tumor protective effects. NPs-TPP-NIT prevented activation of IKK/IκB/NF-κB signaling, reduced secretion of pro-inflammatory factors, and promoted production of anti-inflammatory factors in the spleen, which exhibited radiation-induced damage repair capability without diminishing the therapeutic effect of radiation therapy. It suggests that NPs-TPP-NIT serve as a potential radioprotective drug to shelter immune organs from radiation-induced damage.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"23 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142449859","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":"R-loops’ m6A modification and its roles in cancers","authors":"Yue Qiu, Changfeng Man, Luyu Zhu, Shiqi Zhang, Xiaoyan Wang, Dandan Gong, Yu Fan","doi":"10.1186/s12943-024-02148-y","DOIUrl":"https://doi.org/10.1186/s12943-024-02148-y","url":null,"abstract":"R-loops are three-stranded nucleic acid structures composed of an RNA–DNA hybrid and a displaced DNA strand. They are widespread and play crucial roles in regulating gene expression, DNA replication, and DNA and histone modifications. However, their regulatory mechanisms remain unclear. As R-loop detection technology advances, changes in R-loop levels have been observed in cancer models, often associated with transcription-replication conflicts and genomic instability. N6-methyladenosine (m6A) is an RNA epigenetic modification that regulates gene expression by affecting RNA localization, splicing, translation, and degradation. Upon reviewing the literature, we found that R-loops with m6A modifications are implicated in tumor development and progression. This article summarizes the molecular mechanisms and detection methods of R-loops and m6A modifications in gene regulation, and reviews recent research on m6A-modified R-loops in oncology. Our goal is to provide new insights into the origins of genomic instability in cancer and potential strategies for targeted therapy.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"5 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142448581","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: Identification of TRAIL-inducing compounds highlights small molecule ONC201/TIC10 as a unique anti-cancer agent that activates the TRAIL pathway","authors":"Joshua E Allen, Gabriel Krigsfeld, Luv Patel, Patrick A Mayes, David T Dicker, Gen Sheng Wu, Wafik S El-Deiry","doi":"10.1186/s12943-024-02158-w","DOIUrl":"https://doi.org/10.1186/s12943-024-02158-w","url":null,"abstract":"<p><b>Correction</b><b>: </b><b>Mol Cancer 14, 99 (2015)</b></p><p><b>https://doi.org/10.1186/s12943-015-0346-9</b></p><br/><p>Following publication of the original article [1], the authors reported inadvertent errors in two panels of Figure 3.</p><p>The original Figure 3B shows a duplication of a histological image. The duplicated image has been replaced and the images, as well as their labels, have been accurately arranged in the corrected Figure 3. In addition, the attached corrected Figure 3 revises two time point labels in panel E.</p><p>The following clarification was added to figure legend 3E: “A portion of the control and ONC201/TIC10 results shown for reference were previously published [26].” The corrected and incorrect figures are given below.</p><p>Incorrect Figure 3:</p><figure><picture><source srcset=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-024-02158-w/MediaObjects/12943_2024_2158_Figa_HTML.png?as=webp\" type=\"image/webp\"/><img alt=\"figure a\" aria-describedby=\"Figa\" height=\"743\" loading=\"lazy\" src=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-024-02158-w/MediaObjects/12943_2024_2158_Figa_HTML.png\" width=\"685\"/></picture></figure><p>Correct Figure 3:</p><figure><picture><source srcset=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-024-02158-w/MediaObjects/12943_2024_2158_Figb_HTML.png?as=webp\" type=\"image/webp\"/><img alt=\"figure b\" aria-describedby=\"Figb\" height=\"603\" loading=\"lazy\" src=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-024-02158-w/MediaObjects/12943_2024_2158_Figb_HTML.png\" width=\"685\"/></picture></figure><ol data-track-component=\"outbound reference\" data-track-context=\"references section\"><li data-counter=\"1.\"><p>Allen JE, Krigsfeld G, Patel L, et al. Identification of TRAIL-inducing compounds highlights small molecule ONC201/TIC10 as a unique anti-cancer agent that activates the TRAIL pathway. Mol Cancer. 2015;14:99. https://doi.org/10.1186/s12943-015-0346-9.</p><p>Article PubMed PubMed Central Google Scholar </p></li></ol><p>Download references<svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"><use xlink:href=\"#icon-eds-i-download-medium\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"></use></svg></p><h3>Authors and Affiliations</h3><ol><li><p>Departments of Medicine, Genetics, and Pharmacology, Laboratory of Molecular Oncology and Cell Cycle Regulation, University of Pennsylvania School of Medicine, Philadelphia, 19104, PA, USA</p><p>Joshua E Allen, Gabriel Krigsfeld, Luv Patel, Patrick A Mayes, David T Dicker & Wafik S El-Deiry</p></li><li><p>Current affiliation: Oncoceutics, Inc., Hummelstown, PA, USA</p><p>Joshua E Allen</p></li><li><p>Department of Medical Oncology and Molecular Therapeutics Program, Laboratory of Translational Oncology and Experimental Cancer Therapeutics, Fox Chase Cancer Center, Philadelphia, 19111, PA, USA</p><p>David T Dicker & Wa","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"7 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142448577","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: Acyl-coenzyme a binding protein (ACBP) - a risk factor for cancer diagnosis and an inhibitor of immunosurveillance","authors":"Léa Montégut, Peng Liu, Liwei Zhao, María Pérez-Lanzón, Hui Chen, Misha Mao, Shuai Zhang, Lisa Derosa, Julie Le Naour, Flavia Lambertucci, Silvia Mingoia, Uxía Nogueira-Recalde, Rafael Mena-Osuna, Irene Herranz-Montoya, Nabil Djouder, Sylvain Baulande, Hui Pan, Adrien Joseph, Meriem Messaoudene, Bertrand Routy, Marine Fidelle, Tarek Ben Ahmed, Olivier Caron, Pierre Busson, David Boulate, Mélanie Deschasaux-Tanguy, Nathalie Arnault, Jonathan G. Pol, Eliane Piaggio, Mathilde Touvier, Laurence Zitvogel, Suzette Delaloge, Isabelle Martins, Guido Kroemer","doi":"10.1186/s12943-024-02152-2","DOIUrl":"https://doi.org/10.1186/s12943-024-02152-2","url":null,"abstract":"<p><b>Correction: Mol Cancer 23 187 (2024)</b></p><p><b>https://doi.org/10.1186/s12943-024-02098-5</b></p><p>Following publication of the original article [1], the authors noticed a minor but significant error in the representation of the author name Tarek Ben Ahmed as “Ben” was captured as given name instead of a family name. Thus, in the online version, the name Tarek Ben Ahmed was mistakenly listed as Ahmed TB instead of Ben Ahmed T. The original article has been corrected.</p><ol data-track-component=\"outbound reference\" data-track-context=\"references section\"><li data-counter=\"1.\"><p>Montégut L, Liu P, Zhao L. et al. Acyl-coenzyme a binding protein (ACBP) - a risk factor for cancer diagnosis and an inhibitor of immunosurveillance. Mol Cancer. 2024;23:187. https://doi.org/10.1186/s12943-024-02098-5</p></li></ol><p>Download references<svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"><use xlink:href=\"#icon-eds-i-download-medium\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"></use></svg></p><h3>Authors and Affiliations</h3><ol><li><p>Centre de Recherche des Cordeliers, Université Paris Cité, Sorbonne Université, Equipe labellisée par la Ligue Contre le Cancer, Inserm U1138, Paris, France</p><p>Léa Montégut, Peng Liu, Liwei Zhao, María Pérez-Lanzón, Hui Chen, Misha Mao, Shuai Zhang, Julie Le Naour, Flavia Lambertucci, Silvia Mingoia, Uxía Nogueira-Recalde, Hui Pan, Adrien Joseph, Jonathan G. Pol, Isabelle Martins & Guido Kroemer</p></li><li><p>Metabolomics and Cell Biology Platforms, Gustave Roussy Institut, Villejuif, France</p><p>Léa Montégut, Peng Liu, Liwei Zhao, María Pérez-Lanzón, Hui Chen, Misha Mao, Shuai Zhang, Julie Le Naour, Flavia Lambertucci, Uxía Nogueira-Recalde, Hui Pan, Jonathan G. Pol, Laurence Zitvogel, Isabelle Martins & Guido Kroemer</p></li><li><p>Faculté de Médecine, Université de Paris Saclay, Kremlin Bicêtre, Paris, France</p><p>Léa Montégut, Hui Chen, Lisa Derosa, Julie Le Naour, Hui Pan & Laurence Zitvogel</p></li><li><p>Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China</p><p>Shuai Zhang</p></li><li><p>Equipe Labellisée Par la Ligue Contre le Cancer, Inserm U1015, Gustave Roussy, Villejuif, France</p><p>Lisa Derosa, Marine Fidelle, Laurence Zitvogel & Suzette Delaloge</p></li><li><p>Department of Pharmacological Sciences, University of Piemonte Orientale, Novara, Italia</p><p>Silvia Mingoia</p></li><li><p>Grupo de Investigación en Reumatología (GIR), Instituto de Investigación Biomédica de A Coruña (INIBIC), Fundación Profesor Novoa Santos, A Coruña, Spain</p><p>Uxía Nogueira-Recalde</p></li><li><p>Department of Translational Research, Institute Curie Research Center, INSERM U932, PSL Research University, Paris, France</p><p>Rafael Mena-Osuna & Eliane Piaggio</p></li><li><p>Growth Factors, Nutrients and Cancer Group, Molecular Oncology Programme, Centro Nacional de Inv","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"11 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142443910","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":"Tumor-intrinsic role of ICAM-1 in driving metastatic progression of triple-negative breast cancer through direct interaction with EGFR","authors":"Jae-Hyeok Kang, Nizam Uddin, Seungmo Kim, Yi Zhao, Ki-Chun Yoo, Min-Jung Kim, Sung-Ah Hong, Sangsu Bae, Jeong-Yeon Lee, Incheol Shin, Young Woo Jin, Heather M. O’Hagan, Joo Mi Yi, Su-Jae Lee","doi":"10.1186/s12943-024-02150-4","DOIUrl":"https://doi.org/10.1186/s12943-024-02150-4","url":null,"abstract":"Triple-negative breast cancer (TNBC), the most aggressive subtype, presents a critical challenge due to the absence of approved targeted therapies. Hence, there is an urgent need to identify effective therapeutic targets for this condition. While epidermal growth factor receptor (EGFR) is prominently expressed in TNBC and recognized as a therapeutic target, anti-EGFR therapies have yet to gain approval for breast cancer treatment due to their associated side effects and limited efficacy. Here, we discovered that intercellular adhesion molecule-1 (ICAM-1) exhibits elevated expression levels in metastatic breast cancer and serves as a pivotal binding adaptor for EGFR activation, playing a crucial role in malignant progression. The activation of EGFR by tumor-expressed ICAM-1 initiates biased signaling within the JAK1/STAT3 pathway, consequently driving epithelial-to-mesenchymal transition and facilitating heightened metastasis without influencing tumor growth. Remarkably, ICAM-1-neutralizing antibody treatment significantly suppressed cancer metastasis in a breast cancer orthotopic xenograft mouse model. In conclusion, our identification of ICAM-1 as a novel tumor intrinsic regulator of EGFR activation offers valuable insights for the development of TNBC-specific anti-EGFR therapies.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"75 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142440196","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":"Prostate cancer microenvironment: multidimensional regulation of immune cells, vascular system, stromal cells, and microbiota","authors":"Lin Chen, Yu-Xin Xu, Yuan-Shuo Wang, Ying-Ying Ren, Xue-Man Dong, Pu Wu, Tian Xie, Qi Zhang, Jian-Liang Zhou","doi":"10.1186/s12943-024-02137-1","DOIUrl":"https://doi.org/10.1186/s12943-024-02137-1","url":null,"abstract":"Prostate cancer (PCa) is one of the most prevalent malignancies in males worldwide. Increasing research attention has focused on the PCa microenvironment, which plays a crucial role in tumor progression and therapy resistance. This review aims to provide a comprehensive overview of the key components of the PCa microenvironment, including immune cells, vascular systems, stromal cells, and microbiota, and explore their implications for diagnosis and treatment. Keywords such as “prostate cancer”, “tumor microenvironment”, “immune cells”, “vascular system”, “stromal cells”, and “microbiota” were used for literature retrieval through online databases including PubMed and Web of Science. Studies related to the PCa microenvironment were selected, with a particular focus on those discussing the roles of immune cells, vascular systems, stromal cells, and microbiota in the development, progression, and treatment of PCa. The selection criteria prioritized peer-reviewed articles published in the last five years, aiming to summarize and analyze the latest research advancements and clinical relevance regarding the PCa microenvironment. The PCa microenvironment is highly complex and dynamic, with immune cells contributing to immunosuppressive conditions, stromal cells promoting tumor growth, and microbiota potentially affecting androgen metabolism. Vascular systems support angiogenesis, which fosters tumor expansion. Understanding these components offers insight into the mechanisms driving PCa progression and opens avenues for novel therapeutic strategies targeting the tumor microenvironment. A deeper understanding of the PCa microenvironment is crucial for advancing diagnostic techniques and developing precision therapies. This review highlights the potential of targeting the microenvironment to improve patient outcomes, emphasizing its significance in the broader context of PCa research and treatment innovation. ","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"207 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142415636","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":"Chaperone-mediated autophagy modulates Snail protein stability: implications for breast cancer metastasis.","authors":"Ki-Jun Ryu, Ki Won Lee, Seung-Ho Park, Taeyoung Kim, Keun-Seok Hong, Hyemin Kim, Minju Kim, Dong Woo Ok, Gu Neut Bom Kwon, Young-Jun Park, Hyuk-Kwon Kwon, Cheol Hwangbo, Kwang Dong Kim, J Eugene Lee, Jiyun Yoo","doi":"10.1186/s12943-024-02138-0","DOIUrl":"10.1186/s12943-024-02138-0","url":null,"abstract":"<p><p>Breast cancer remains a significant health concern, with triple-negative breast cancer (TNBC) being an aggressive subtype with poor prognosis. Epithelial-mesenchymal transition (EMT) is important in early-stage tumor to invasive malignancy progression. Snail, a central EMT component, is tightly regulated and may be subjected to proteasomal degradation. We report a novel proteasomal independent pathway involving chaperone-mediated autophagy (CMA) in Snail degradation, mediated via its cytosolic interaction with HSC70 and lysosomal targeting, which prevented its accumulation in luminal-type breast cancer cells. Conversely, Snail predominantly localized to the nucleus, thus evading CMA-mediated degradation in TNBC cells. Starvation-induced CMA activation downregulated Snail in TNBC cells by promoting cytoplasmic translocation. Evasion of CMA-mediated Snail degradation induced EMT, and enhanced metastatic potential of luminal-type breast cancer cells. Our findings elucidate a previously unrecognized role of CMA in Snail regulation, highlight its significance in breast cancer, and provide a potential therapeutic target for clinical interventions.</p>","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"23 1","pages":"227"},"PeriodicalIF":27.7,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11468019/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Size matters: integrating tumour volume and immune activation signatures predicts immunotherapy response","authors":"Su Yin Lim, Ines Pires da Silva, Nurudeen A. Adegoke, Serigne N. Lo, Alexander M. Menzies, Matteo S. Carlino, Richard A. Scolyer, Georgina V. Long, Jenny H. Lee, Helen Rizos","doi":"10.1186/s12943-024-02146-0","DOIUrl":"https://doi.org/10.1186/s12943-024-02146-0","url":null,"abstract":"Immune checkpoint inhibitors (ICIs) have transformed cancer treatment, providing significant benefit to patients across various tumour types, including melanoma. However, around 40% of melanoma patients do not benefit from ICI treatment, and accurately predicting ICI response remains challenging. We now describe a novel and simple approach that integrates immune-associated transcriptome signatures and tumour volume burden to better predict ICI response in melanoma patients. RNA sequencing was performed on pre-treatment (PRE) tumour specimens derived from 32 patients with advanced melanoma treated with combination PD1 and CTLA4 inhibitors. Of these 32 patients, 11 also had early during treatment (EDT, 5–15 days after treatment start) tumour samples. Tumour volume was assessed at PRE for all 32 patients, and at first computed tomography (CT) imaging for the 11 patients with EDT samples. Analysis of the Hallmark IFNγ gene set revealed no association with ICI response at PRE (AUC ROC curve = 0.6404, p = 0.24, 63% sensitivity, 71% specificity). When IFNg activity was evaluated with tumour volume (ratio of gene set expression to tumour volume) using logistic regression to predict ICI response, we observed high discriminative power in separating ICI responders from non-responders (AUC = 0.7760, p = 0.02, 88% sensitivity, 67% specificity); this approach was reproduced with other immune-associated transcriptomic gene sets. These findings were further replicated in an independent cohort of 23 melanoma patients treated with PD1 inhibitor. Hence, integrating tumour volume with immune-associated transcriptomic signatures improves the prediction of ICI response, and suggest that higher levels of immune activation relative to tumour burden are required for durable ICI response.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"59 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142405205","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}