Molecular Cancer最新文献

{"title":"Clinical approaches to overcome PARP inhibitor resistance","authors":"Yutian Zou, Hanqi Zhang, Pangzhou Chen, Jiayi Tang, Siwei Yang, Christophe Nicot, Ziyun Guan, Xing Li, Hailin Tang","doi":"10.1186/s12943-025-02355-1","DOIUrl":"https://doi.org/10.1186/s12943-025-02355-1","url":null,"abstract":"PARP inhibitors have profoundly changed treatment options for cancers with homologous recombination repair defects, especially those carrying BRCA1/2 mutations. However, the development of resistance to these inhibitors presents a significant clinical challenge as it limits long-term effectiveness. This review provides an overview of the current understanding of resistance mechanisms to PARP inhibitors and explores strategies to overcome these challenges. We discuss the basis of synthetic lethality induced by PARP inhibitors and detail diverse resistance mechanisms affecting PARP inhibitors, including homologous recombination restoration, reduced PARP trapping, enhanced drug efflux, and replication fork stabilization. The review then considers clinical approaches to combat resistance, focusing on combination therapies with immune checkpoint inhibitors, DNA damage response inhibitors, and epigenetic drugs. We also highlight ongoing clinical trials and potential biomarkers for predicting treatment response and resistance. The review concludes by outlining future research directions, emphasizing the need for longitudinal studies, advanced resistance monitoring technologies, and the development of novel combination strategies. By tackling PARP inhibitor resistance, this review seeks to aid in the development of more effective cancer therapies, with the potential to improve outcomes for patients with homologous recombination-deficient tumors.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"82 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144176547","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":"Targeting metastasis in paediatric bone sarcomas","authors":"Emma C. Bull, Archana Singh, Amy M. Harden, Kirsty Soanes, Hala Habash, Lisa Toracchio, Marianna Carrabotta, Christina Schreck, Karan M. Shah, Paulina Velasco Riestra, Margaux Chantoiseau, Maria Eugénia Marques Da Costa, Gaël Moquin-Beaudry, Pan Pantziarka, Edidiong Akanimo Essiet, Craig Gerrand, Alison Gartland, Linda Bojmar, Anna Fahlgren, Antonin Marchais, Evgenia Papakonstantinou, Eleni M. Tomazou, Didier Surdez, Dominique Heymann, Florencia Cidre-Aranaz, Olivia Fromigue, Darren W. Sexton, Nikolas Herold, Thomas G. P. Grünewald, Katia Scotlandi, Michaela Nathrath, Darrell Green","doi":"10.1186/s12943-025-02365-z","DOIUrl":"https://doi.org/10.1186/s12943-025-02365-z","url":null,"abstract":"Paediatric bone sarcomas (e.g. Ewing sarcoma, osteosarcoma) comprise significant biological and clinical heterogeneity. This extreme heterogeneity affects response to systemic therapy, facilitates inherent and acquired drug resistance and possibly underpins the origins of metastatic disease, a key component implicit in cancer related death. Across all cancers, metastatic models have offered competing accounts on when dissemination occurs, either early or late during tumorigenesis, whether metastases at different foci arise independently and directly from the primary tumour or give rise to each other, i.e. metastases-to-metastases dissemination, and whether cell exchange occurs between synchronously growing lesions. Although it is probable that all the above mechanisms can lead to metastatic disease, clinical observations indicate that distinct modes of metastasis might predominate in different cancers. Around 70% of patients with bone sarcoma experience metastasis during their disease course but the fundamental molecular and cell mechanisms underlying spread are equivocal. Newer therapies such as tyrosine kinase inhibitors have shown promise in reducing metastatic relapse in trials, nonetheless, not all patients respond and 5-year overall survival remains at ~ 50%. Better understanding of potential bone sarcoma biological subgroups, the role of the tumour immune microenvironment, factors that promote metastasis and clinical biomarkers of prognosis and drug response are required to make progress. In this review, we provide a comprehensive overview of the approaches to manage paediatric patients with metastatic Ewing sarcoma and osteosarcoma. We describe the molecular basis of the tumour immune microenvironment, cell plasticity, circulating tumour cells and the development of the pre-metastatic niche, all required for successful distant colonisation. Finally, we discuss ongoing and upcoming patient clinical trials, biomarkers and gene regulatory networks amenable to the development of anti-metastasis medicines.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"161 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144165258","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":"GP73-dependent regulation of exosome biogenesis promotes colorectal cancer liver metastasis.","authors":"Linfei Huang,Meng Wei,Huilong Li,Mingxin Yu,Luming Wan,Ruzhou Zhao,Qi Gao,Lijuan Sun,Xufeng Hou,Yunhai Mo,Qing Huang,Lan Zhen,Xiaopan Yang,Jingfei Li,Nan Wang,Chundong Zhang,Haoran Jin,Li Zhou,Yixin Xu,Haotian Lin,Xuhui Zhang,Boan Li,Yue Han,Jing Yuan,Rui Zhang,Feixiang Wu,Hui Zhong,Congwen Wei","doi":"10.1186/s12943-025-02350-6","DOIUrl":"https://doi.org/10.1186/s12943-025-02350-6","url":null,"abstract":"Colorectal cancer (CRC) liver metastasis is the main cause of cancer-related mortality. How liver influences intercellular communication to support CRC liver metastasis remains unknown. Herein, we link GP73, whose chronic upregulation in hepatocytes triggers non-obese metabolic-dysfunction associated steatotic liver disease (MASLD) in mice, with exosome biogenesis and CRC liver metastasis. Mice with high liver GP73 expression exhibited increased CRC liver metastasis in an exosome-dependent manner. GP73 modulated the cholesterol contents in endosomal compartments to promote exosome production. Quantitative proteomics revealed GP73 reshaped hepatocyte exosomal proteome and produced NAV2-rich exosomes. Clinically, serum GP73 levels positively correlated with exosomal NAV2 levels in CRC patients with liver metastasis. Knockdown of liver NAV2 suppressed enhanced CRC liver metastasis in GP73-induced non-obese mice, and GP73 blockade mitigated the increased CRC liver metastasis in obese mice fed by high-fat diet or high-fructose diet. Our findings suggest GP73 blockade as a potential therapeutic strategy for mitigating CRC liver metastasis.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"45 1","pages":"151"},"PeriodicalIF":37.3,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144136657","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":"NAP1L1 degradation by FBXW7 reduces the deubiquitination of HDGF-p62 signaling to stimulate autophagy and induce primary cisplatin chemosensitivity in nasopharyngeal carcinoma.","authors":"Bin Gong,Yahui Liu,Weiwei Yan,Chao Cheng,Huiling Yang,Jiyu Huang,Qing Liu,Yuyan Liu,Jiankang Guo,Xiaojie Deng,Beixian Zhou,Dayong Zheng,Xiong Liu,Zhen Liu,Weiyi Fang","doi":"10.1186/s12943-025-02349-z","DOIUrl":"https://doi.org/10.1186/s12943-025-02349-z","url":null,"abstract":"Nucleosome assembly protein 1-like 1 (NAP1L1) has been implicated in promoting tumor cell proliferation. However, its role in regulating autophagy in tumors, including nasopharyngeal carcinoma (NPC), remains unclear. In this study, we observed that autophagy-inducing agents reduced NAP1L1 protein levels without affecting its mRNA expression. Reduced NAP1L1 enhanced autophagosome formation and maturation, thereby promoting cisplatin (DDP) chemosensitivity in both in vitro and in vivo NPC models. Mechanistically, reduced NAP1L1 impaired the recruitment of ubiquitin-specific protease 14 (USP14), limiting the deubiquitination of heparin-binding growth factor (HDGF) and decreasing HDGF protein levels. In turn, reduced HDGF suppressed USP14-mediated p62 deubiquitination, leading to further declines in p62 protein levels. Notably, the F-box and WD repeat domain-containing protein 7 (FBXW7), an inhibitory E3 ubiquitin ligase, directly interacted with and ubiquitinated NAP1L1, promoting its degradation. This degradation triggered NPC autophagy and enhanced DDP chemosensitivity by disrupting NAP1L1-induced HDGF/p62 signaling. Clinically, NAP1L1 protein expression was inversely correlated with FBXW7 levels in NPC tissue samples. Patients exhibiting high NAP1L1 and low FBXW7 levels had the poorest DDP chemosensitivity and survival outcomes. Our findings demonstrate that FBXW7-mediated NAP1L1 degradation suppresses HDGF-p62 signaling, thereby inducing autophagy and enhancing DDP chemosensitivity. These results underscore the potential of NAP1L1 and FBXW7 as therapeutic targets for NPC treatment.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"24 1","pages":"152"},"PeriodicalIF":37.3,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144136654","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":"Drug-induced tolerant persisters in tumor: mechanism, vulnerability and perspective implication for clinical treatment","authors":"Shujie Liu, Anfeng Jiang, Faqing Tang, Minghao Duan, Bin Li","doi":"10.1186/s12943-025-02323-9","DOIUrl":"https://doi.org/10.1186/s12943-025-02323-9","url":null,"abstract":"Cancer remains a significant global health burden due to its high morbidity and mortality. Oncogene-targeted therapy and immunotherapy have markedly improved the 5-year survival rate in the patients with advanced or metastatic tumors compared to outcomes in the era of chemotherapy/radiation. Nevertheless, the majority of patients remain incurable. Initial therapies eliminate the bulk of tumor cells, yet residual populations termed drug-tolerant persister cells (DTPs) survive, regenerate tumor and even drive distant metastases. Notably, DTPs frequently render tumor cross-resistance, a detrimental phenomenon observed in the patients with suboptimal responses to subsequent therapies. Analogous to species evolution, DTPs emerge as adaptative products at the cellular level, instigated by integrated intracellular stress responses to therapeutic pressures. These cells exhibit profound heterogeneity and adaptability shaped by the intricate feedforward loops among tumor cells, surrounding microenvironments and host ecology, which vary across tumor types and therapeutic regimens. In this review, we revisit the concept of DTPs, with a focus on their generation process upon targeted therapy or immunotherapy. We dissect the critical phenotypes and molecule mechanisms underlying DTPs to therapy from multiple aspects, including intracellular events, intercellular crosstalk and the distant ecologic pre-metastatic niches. We further spotlight therapeutic strategies to target DTP vulnerabilities, including synthetic lethality approaches, adaptive dosing regimens informed by mathematical modeling, and immune-mediated eradication. Additionally, we highlight synergistic interventions such as lifestyle modifications (e.g., exercise, stress reduction) to suppress pro-tumorigenic inflammation. By integrating mechanistic insights with translational perspectives, this work bridges the gap between DTP biology and clinical strategies, aiming for optimal efficacy and preventing relapse.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"133 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144130297","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":"LMTK3 regulation of EV biogenesis and cargo sorting promotes tumour growth by reducing monocyte infiltration and driving pro-tumourigenic macrophage polarisation in breast cancer.","authors":"Mark Samuels,Christos Karakostas,Simoni Besta,Andrea Lauer Betrán,Katerina Tsilingiri,Charlotte Turner,Reza Shirazi Nia,Niloufar Poudine,Richard Goodyear,William Jones,Apostolos Klinakis,Georgios Giamas","doi":"10.1186/s12943-025-02346-2","DOIUrl":"https://doi.org/10.1186/s12943-025-02346-2","url":null,"abstract":"BACKGROUNDLemur Tail Kinase 3 (LMTK3) promotes cell proliferation, invasiveness and therapy resistance, and its expression correlates with poor survival in several different malignancies, including breast cancer. Crosstalk through extracellular vesicles (EVs) is an increasingly appreciated mechanism of cell communication within the tumour immune microenvironment, which contributes to different aspects of cancer progression and plays a pivotal role in shaping tumour fate.METHODSNanoparticle tracking analysis and transmission electron microscopy were used to study the effects of LMTK3 on EV size, while single particle interferometry allowed us to examine LMTK3-dependent effects on the subpopulation distribution of EVs. Quantitative mass spectrometry was used to profile LMTK3-dependent proteomics changes in breast cancer-derived EVs. Bioinformatics analysis of clinical data along with in vitro and cell-based assays were implemented to explore the effects of LMTK3-dependent EV protein cargo on the tumour immune microenvironment. To elucidate the mechanism through which LMTK3 impacts endosomal trafficking and regulates EV biogenesis, we used a variety of approaches, including in vitro kinase assays, confocal and electron microscopy, as well as in vivo subcutaneous and orthotopic breast cancer mouse models.RESULTSHere, we report that LMTK3 increases the average size of EVs, modulates immunoregulatory EV proteomic cargo and alters the subpopulation distribution of EVs released by breast cancer cells. Mechanistically, we provide evidence that LMTK3 phosphorylates Rab7, a key regulator of multivesicular body (MVB) trafficking, thereby reducing the fusion of MVBs with lysosomes and subsequent degradation of intralumenal vesicles, resulting in altered EV release. Moreover, LMTK3 causes increased packaging of phosphoserine aminotransferase 1 (PSAT1) in EVs, leading to a paracrine upregulation of phosphoglycerate dehydrogenase (PHGDH) in monocytes when these EVs are taken up. PSAT1 and PHGDH play key roles in the serine biosynthesis pathway, which is closely linked to cancer progression and regulation of monocyte behaviour. LMTK3 EV-induced elevated PHGDH expression in monocytes reduces their infiltration into breast cancer 3D spheroids and in vivo breast cancer mouse models. Furthermore, these infiltrating monocytes preferentially differentiate into pro-tumourigenic M2-like macrophages. Additional breast cancer mouse studies highlight the contribution of LMTK3-dependent EVs in the observed immunosuppressive macrophage phenotype. Finally, in vitro experiments show that pharmacological inhibition of LMTK3 reverses the pro-tumourigenic and immunomodulatory effects mediated by EVs derived from LMTK3 overexpressing cells.CONCLUSIONOverall, this study advances our knowledge on the mechanisms of EV biogenesis and highlights a novel oncogenic role of LMTK3 in the breast TME, further supporting it as a target for cancer therapy.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"130 1","pages":"149"},"PeriodicalIF":37.3,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144122049","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":"Biofilm formation by the host microbiota: a protective shield against immunity and its implication in cancer","authors":"Elena Montanari, Giancarla Bernardo, Valentino Le Noci, Martina Anselmi, Serenella M. Pupa, Elda Tagliabue, Michele Sommariva, Lucia Sfondrini","doi":"10.1186/s12943-025-02348-0","DOIUrl":"https://doi.org/10.1186/s12943-025-02348-0","url":null,"abstract":"Human-resident microbes typically cluster into biofilms - structurally organized communities embedded within a matrix of self-produced extracellular polymeric substance (EPS) that serves as a protective shield. These biofilms enhance microbial survival and functional adaptability, favoring a symbiotic relationship with the host under physiological conditions. However, biofilms exhibit a dual role in modulating the immune response. If their ability to promote tolerance is key to safeguarding homeostasis, by contrast, their persistence can overcome the cutting-edge balance resulting in immune evasion, chronic inflammation and development of numerous diseases such as cancer. Recent evidence highlights the significance of cancer-associated microbiota in shaping the tumor microenvironment (TME). These microbial inhabitants often exhibit biofilm-like structures, which may protect them from host immune responses and therapeutic interventions. The presence of biofilm-forming microbiota within the TME may promote chronic inflammation, and release of bioactive molecules that interfere with immune surveillance mechanisms, thereby enabling cancer cells to evade immune destruction. This review delves into the complex interplay between biofilms and cancer, with particular focus on the tumor-associated microbiota and the implications of biofilm involvement in modulating the immune landscape of the TME. Addressing this intricate relationship holds promises for innovative therapeutic approaches aimed at reprogramming the microbiota-cancer axis for better clinical outcomes. ","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"32 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144104580","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":"Double-sided niche regulation in skin stem cell and cancer: mechanisms and clinical applications","authors":"Trang Thao Quoc Pham, Yung-Che Kuo, Wei-Ling Chang, Hao-Jui Weng, Yen-Hua Huang","doi":"10.1186/s12943-025-02289-8","DOIUrl":"https://doi.org/10.1186/s12943-025-02289-8","url":null,"abstract":"The niche microenvironment plays a crucial role in regulating the fate of normal skin stem cells (SSCs) and cancer stem cells (CSCs). Therapeutically targeting the CSC niche holds promise as an effective strategy; however, the dual effects of shared SSC niche signaling in CSCs have contributed to the aggressive characteristics of tumors and poor survival rates in skin cancer patients. The lack of a clear underlying mechanism has significantly hindered drug development for effective treatment. This article explores recent advances in understanding how niche factors regulate cell fate determination between skin stem cells and skin CSCs, along with their clinical implications. The dual roles of key components of the adhesive niche, including the dermo-epidermal junction and adherens junction, various cell types—especially immune cells and fibroblasts—as well as major signaling pathways such as Sonic hedgehog (Shh), Wingless-related integration site (Wnt)/β-catenin, YAP (Yes-associated protein)/TAZ (transcriptional coactivator with PDZ-binding motif), and Notch, are highlighted. Additionally, recent advances in clinical trials and drug development targeting these pathways are discussed. Overall, this review provides valuable insights into the complex interactions between skin cancer stem cells and their microenvironment, laying the groundwork for future research and clinical strategies.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"38 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144104539","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: CircDIDO1 inhibits gastric cancer progression by encoding a novel DIDO1‑529aa protein and regulating PRDX2 protein stability","authors":"Yu Zhang, Jiajia Jiang, Jiayin Zhang, Han Shen, Maoye Wang, Zhen Guo, Xueyan Zang, Hui Shi, Jiayan Gao, Hui Cai, Xinjian Fang, Hui Qian, Wenrong Xu, Xu Zhang","doi":"10.1186/s12943-025-02356-0","DOIUrl":"https://doi.org/10.1186/s12943-025-02356-0","url":null,"abstract":"<p><b>Correction</b><b>: </b><b>Mol Cancer 20, 101 (2021)</b></p><p><b>https://doi.org/10.1186/s12943-021-01390-y</b></p><br/><p>Following the publication of the original article [1], the authors have identified two layout-related errors that occurred during the figure assembly or production process. In Figure 2d, the images for the MGC-803 cell invasion assay were inadvertently misplaced. In Additional file 1: Supplementary Figure 1e, the MGC-803 cell invasion assay images were also affected by a similar layout error. The incorrect and correct figure is provided below. The Supplementary Figure 1 has been updated in the Supplementary Information section of this correction note article.</p><p>Incorrect Figure 2:</p><figure><picture><source srcset=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-025-02356-0/MediaObjects/12943_2025_2356_Figa_HTML.png?as=webp\" type=\"image/webp\"/><img alt=\"figure a\" aria-describedby=\"Figa\" height=\"830\" loading=\"lazy\" src=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-025-02356-0/MediaObjects/12943_2025_2356_Figa_HTML.png\" width=\"685\"/></picture></figure><p>Correct Figure 2:</p><figure><picture><source srcset=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-025-02356-0/MediaObjects/12943_2025_2356_Figb_HTML.png?as=webp\" type=\"image/webp\"/><img alt=\"figure b\" aria-describedby=\"Figb\" height=\"783\" loading=\"lazy\" src=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12943-025-02356-0/MediaObjects/12943_2025_2356_Figb_HTML.png\" width=\"685\"/></picture></figure><ol data-track-component=\"outbound reference\" data-track-context=\"references section\"><li data-counter=\"1.\"><p>Zhang Y, Jiang J, Zhang J, et al. CircDIDO1 inhibits gastric cancer progression by encoding a novel DIDO1-529aa protein and regulating PRDX2 protein stability. Mol Cancer. 2021;20:101. https://doi.org/10.1186/s12943-021-01390-y.</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><span>Author notes</span><ol><li><p>Yu Zhang and Jiajia Jiang contributed equally to this work.</p></li></ol><h3>Authors and Affiliations</h3><ol><li><p>Aoyang Cancer Institute, Affiliated Aoyang Hospital of Jiangsu University, Zhangjiagang, 215600, Jiangsu, China</p><p>Yu Zhang, Jiajia Jiang, Jiayin Zhang, Maoye Wang, Zhen Guo, Xueyan Zang, Hui Shi, Jiayan Gao, Hui Qian, Wenrong Xu & Xu Zhang</p></li><li><p>Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, 212013, Jiangsu, China</p><p>Yu Zhang, Jiajia Jiang, Jiayin Zhang, Han Shen, Maoye Wang, Zhen Guo, Xueyan Zang, Hui Shi, Hui Qian, Wenrong Xu & Xu Zhang</p></li><li><p>Department of Laboratory Medicine, Nanjing Drum Tower Hospital, ","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"22 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144104540","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":"SLAMF receptors: key regulators of tumor progression and emerging targets for cancer immunotherapy","authors":"Jia Li, Tao Fan, Di Wang, Chu Xiao, Ziqin Deng, Wenpeng Cai, Yu Ji, Chunxiang Li, Jie He","doi":"10.1186/s12943-025-02308-8","DOIUrl":"https://doi.org/10.1186/s12943-025-02308-8","url":null,"abstract":"The signaling lymphocytic activation molecule family (SLAMF) consists of nine distinct cell surface receptors predominantly expressed on immune cells, each characterized by unique structural features, expression patterns, downstream signaling pathways, and biological functions. These receptors play critical roles in modulating various immune cell activities within the tumor microenvironment, thereby shaping immune responses in cancer. Although accumulating evidence demonstrates their value as therapeutic targets for developing cancer immunotherapies, the full spectrum of SLAMF receptors in cancer remains incompletely understood. This review aims to provide a comprehensive overview of the molecular characteristics and immunomodulatory functions of each SLAMF receptor, underscoring their pivotal contributions to cancer progression. Furthermore, we also highlight their potential as promising targets for advancing cancer immunotherapeutic strategies. Finally, we discuss clinical trials evaluating the efficacy and safety of SLAMF receptor-based immunotherapies, emphasizing their translational relevance in the development of cancer treatments.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"16 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144066791","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}