Molecular Cancer Research最新文献

{"title":"Genomic Profile and Clinicopathologic Analyses of Wild-Type Gastrointestinal Stromal Tumors.","authors":"Lin Sun, Jiaxin Li, Huimin Liu, Jing Chen, Shihui Wang, Rui Deng, Yan Sun","doi":"10.1158/1541-7786.MCR-25-0524","DOIUrl":"10.1158/1541-7786.MCR-25-0524","url":null,"abstract":"<p><p>The driver genes of wild-type gastrointestinal stromal tumors (WT-GIST), particularly quadruple WT-GISTs (qWT-GIST), remain unclear. In this study, we collected 119 WT-GISTs from two cohorts and analyzed their clinicopathologic and genomic features, particularly for qWT-GISTs. Next-generation sequencing (NGS) revealed several fusion genes and gene mutations, such as ARID1B, SETD2, and PLCG2, in qWT-GISTs. Further integrated Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed significantly enriched signaling pathways in qWT-GISTs, including the hypoxia-inducible factor-1 (HIF-1). For qWT-GISTs, large tumors or a high mitotic index prompted a shorter recurrence-free survival (RFS) and a high mitotic index or involvement of the HIF-1 pathway prompted a shorter overall survival (OS); however, neither RFS nor OS was prolonged by postoperative adjuvant therapy. In addition, compared with succinate dehydrogenase complex (SDH)-deficient GISTs, qWT-GISTs were less frequently found in the stomach and less frequently presented as high mitotic index; compared with RAS-related GISTs, qWT-GISTs were more frequently found in the stomach. Stratified analyses showed, in patients with low recurrence risk, qWT-GISTs had better RFS than SDH-deficient GISTs. In patients with high recurrence risk or with postoperative adjuvant therapy, qWT-GISTs presented worse OS than SDH-deficient GISTs. In summary, qWT-GISTs exhibited unique clinicopathologic characteristics and outcomes compared with SDH-deficient and RAS-related GISTs, suggesting that they should be managed using different treatment and follow-up strategies, especially stratified management. Considering the rarity and heterogeneity of WT-GISTs, a regulatory detection procedure should be established for WT-GISTs, including NGS for qWT-GISTs, to identify the molecular mechanisms and potential therapeutic targets.</p><p><strong>Implications: </strong>WT-GISTs are heterogenous tumors which should be managed using different treatments and follow-up strategies.</p>","PeriodicalId":19095,"journal":{"name":"Molecular Cancer Research","volume":" ","pages":"232-241"},"PeriodicalIF":4.7,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145669080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"circNEIL3 Stabilizes SPI1 mRNA and Promotes Glioma Progression and Temozolomide Resistance by Binding to U2AF2.","authors":"Zhi Xue, Qian Peng, Zhonghao Liu, Shengli Sun","doi":"10.1158/1541-7786.MCR-25-0321","DOIUrl":"10.1158/1541-7786.MCR-25-0321","url":null,"abstract":"<p><p>Temozolomide (TMZ) resistance is an urgent problem in the treatment of glioma. circNEIL3 is related to the malignant progression of glioma. Nevertheless, the function of circNEIL3 in TMZ resistance is still unclear. In this study, we found that circNEIL3 is overexpressed in glioma tissues and cells and is related to TMZ resistance. Cell experiments and mouse experiments have shown that inhibiting the expression of circNEIL3 can enhance the sensitivity of glioma cells to TMZ. RNA immunoprecipitation and other molecular experiments demonstrated that circNEIL3 and the RNA-binding protein U2 small nuclear RNA auxiliary factor 2 (U2AF2) interact with each other and partially colocalize in cells. SPI1 was highly expressed in glioma, more significantly in TMZ-resistant tissues, and correlated with circNEIL3 expression. Furthermore, we discovered that U2AF2 interacts with SPI1 mRNA as well, and circNEIL3 and U2AF2 together regulate the expression and mRNA stability of SPI1. More importantly, SPI1 silencing inhibited the malignant progression of cells and partially reversed the effects of circNEIL3 on glioma cell proliferation and apoptosis. In conclusion, circNEIL3 stabilizes SPI1 mRNA expression by binding to U2AF2, thereby promoting glioma progression and TMZ resistance.</p><p><strong>Implications: </strong>Our findings offer new mechanistic insights into glioma drug resistance, and targeting the circNEIL3/U2AF2/SPI1 axis represents a promising approach to counteract TMZ resistance in gliomas.</p>","PeriodicalId":19095,"journal":{"name":"Molecular Cancer Research","volume":" ","pages":"283-292"},"PeriodicalIF":4.7,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145775138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetically Engineered Human iPS Cell-Derived Kidney Organoid Recapitulates an Early Stage of ALK Fusion Gene-Associated Renal Tumorigenesis.","authors":"Go Noguchi, Masaya Baba, Shinji Ohtake, Ryosuke Jikuya, Taku Mitome, Sachi Kawaura, Kota Aomori, Yasuhiro Iribe, Hirotaka Nagasaka, Luh Ade Wilan Krisna, Shintaro Funasaki, Erika Muraoka, Satoshi Fujii, Toyonori Tsuzuki, Ikuma Kato, Mitsuko Furuya, Yoji Nagashima, Hidekazu Nishizawa, Tomomi Kamba, Shohei Kuraoka, Tatsukata Kawagoe, Nobuhisa Mizuki, Tomoyuki Tatenuma, Daiki Ueno, Takashi Kawahara, Hiroki Ito, Mitsuru Komeya, Yusuke Ito, Kentaro Muraoka, Hiroji Uemura, Tomohiko Tamura, Takehiko Ogawa, Toshio Suda, Masahiro Yao, Kazuhide Makiyama, Hidewaki Nakagawa, Brian M Shuch, Christopher J Ricketts, Laura S Schmidt, W Marston Linehan, Ryuichi Nishinakamura, Hisashi Hasumi","doi":"10.1158/1541-7786.MCR-25-0043","DOIUrl":"10.1158/1541-7786.MCR-25-0043","url":null,"abstract":"<p><p>Although kidney cancer arises from a variety of nephron cells with diverse characteristics and develops intratumor heterogeneity, a model to elucidate these complexities is incompletely developed. In this study, we report a genetically engineered human induced pluripotent stem cell-derived kidney organoid (HKO) model, which may recapitulate an early stage of renal tumorigenesis. When we overexpressed the VCL-ALK fusion gene, a renal oncogene, in HKO, tubular cells proliferated, and this proliferation was sustained under long-term culture or hypoxic conditions. In addition, the proliferating tubular cells migrated into the renal parenchyma of host mice upon transplantation. The deconvolution analysis and IHC revealed that the proliferating tubular cells could be arrested at an immature tubular progenitor stage with increased expressions of LIM homeobox protein 1 and jagged canonical Notch ligand 1, critical regulators of nephrogenesis. Our HKO model advances our understanding of renal tumorigenesis in the context of the trajectory of nephron development.</p><p><strong>Implications: </strong>Dysregulated nephron developmental machinery leads to aberrant cell proliferation of immature renal tubules.</p>","PeriodicalId":19095,"journal":{"name":"Molecular Cancer Research","volume":" ","pages":"221-231"},"PeriodicalIF":4.7,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145805056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Landscape of Allele-Specific Expression in Prostate Cancer Reveals Recurrent, Stage-Specific Events in AR Signaling and Resistance Pathways.","authors":"Margaret Tsui, Kevin Hu, Hanbing Song, Sarah C Hsu, Yih-An Chen, Lorraine Nuniz, Julia H Pham, Chih-Hao Chang, Keliana S F Hui, David A Quigley, Jingjing Li, Franklin W Huang","doi":"10.1158/1541-7786.MCR-25-0754","DOIUrl":"10.1158/1541-7786.MCR-25-0754","url":null,"abstract":"<p><p>The effects of cis-regulatory alterations in prostate cancer are insufficiently characterized, presenting an opportunity to discover driver genes and therapeutic targets. To comprehensively study these effects, we identify genes undergoing allele-specific expression (ASE) in localized prostate cancer and metastatic castration-resistant prostate cancer (mCRPC) samples. By defining recurrent ASE events across prostate tissue and tumor-enriched ASE, we develop CASEDI, a computational framework for prioritizing cancer drivers by integrating ASE and clinical data. CASEDI reveals genes showing recurrent ASE and altered expression in prostate cancer, including AR-regulated and oncogenic ACSM1. mCRPC samples show enrichment of ASE in DNA repair, resistance pathways, and oncogenes and increased frequency of monoallelic expression (MAE) compared with localized tumors. We define an mCRPC gene signature based on MAE status that identifies a subgroup of localized patients with worse prognosis. Using ASE analysis, we expand the landscape of cis-regulatory events in prostate cancer to inform the identification of additional therapeutic targets.</p><p><strong>Implications: </strong>This study develops a framework for identifying cancer drivers using prostate cancer ASE data, generates a comprehensive dataset of ASE in prostate cancer and highlights candidate targets in tumorigenesis and metastasis.</p>","PeriodicalId":19095,"journal":{"name":"Molecular Cancer Research","volume":" ","pages":"242-257"},"PeriodicalIF":4.7,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13007663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145990109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MIG-6 Regulates HDAC1-Mediated Angiogenesis and Tumorigenesis in PTEN-Deficient Endometrioid Endometrial Cancer.","authors":"Shamsun Nahar, Jiyoung Yu, Haeam Lee, Dinh Nam Tran, Rong Li, Tae Hoon Kim, Jin-Seok Jung, Kyunggon Kim, Jung-Yoon Yoo, Jae-Wook Jeong","doi":"10.1158/1541-7786.MCR-25-0544","DOIUrl":"10.1158/1541-7786.MCR-25-0544","url":null,"abstract":"<p><p>Endometrioid endometrial cancer (EEC) is the most prevalent gynecologic malignancy, yet no targeted therapies are currently approved by the FDA specifically for it. To identify therapeutic targets for EEC, we performed transcriptomic and proteomic analyses in genetically engineered preclinical cancer models, including uterine-specific phosphatase and tensin homolog (Pten)-deficient (Ptend/d) mice and Ptend/d mice with additional overexpression of the tumor suppressor mitogen-inducible gene 6 (Mig-6) that develop EEC. Transcriptomic analysis revealed significant inhibition of immune, inflammatory, and angiogenesis pathways, with hypoxia-inducible factor-1α (HIF1α) as a key upstream regulator. Interactome and immunoprecipitation analyses identified HDAC1 as a MIG-6-interacting protein that mediates angiogenic signaling in PTEN-deficient endometrial cancer. MIG-6 overexpression suppressed HDAC1 activity and downstream HIF1α-driven angiogenesis. Pharmacologic inhibition of HDAC1 with panobinostat recapitulated the tumor-suppressive effects observed with MIG-6 overexpression. These findings suggest that HDAC1 may represent a potential therapeutic target in EEC and that HDAC inhibition can attenuate early tumor progression and angiogenic signaling in preclinical models.</p><p><strong>Implications: </strong>This study identifies the MIG-6-HDAC1 axis as a key regulator of angiogenesis in EEC, highlighting HDAC1 inhibition as a promising targeted therapeutic strategy for early tumor suppression.</p>","PeriodicalId":19095,"journal":{"name":"Molecular Cancer Research","volume":" ","pages":"258-269"},"PeriodicalIF":4.7,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12935093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146011374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interaction of NDRG1 and TGM2 modulates DNA replication and repair.","authors":"Hanna M Doh, Nina Kozlova, Kayla A Cruz, Taru Muranen","doi":"10.1158/1541-7786.MCR-25-0743","DOIUrl":"10.1158/1541-7786.MCR-25-0743","url":null,"abstract":"<p><p>In tumor cells, DNA replication is constantly challenged by endogenous and exogenous sources, referred to as replication stress, and various pathways have evolved to mitigate this stress in cancer. We recently identified a novel extracellular matrix-induced DNA repair pathway involving NDRG1 (N-myc downstream regulated gene 1). Matrix-induced signaling results in NDRG1-dependent protection from chemotherapy-induced replication stress. To uncover further mechanistic details of NDRG1-mediated effects on DNA replication, we identified Transglutaminase 2 (TGM2) as a novel NDRG1 binding partner. TGM2 is an acyltransferase that catalyzes Ca(2+)-dependent protein modifications. This interaction was enriched upon chemotherapy-induced replication stress and also upon ECM-induced signaling. Our data show that TGM2 depletion significantly slows replication fork progression, and this phenotype is dependent on TGM2 catalytic activity and its nuclear localization. Our study further identified a putative NDRG1-TGM2 binding site and show that the physical interaction between NDRG1 and TGM2 is required for efficient DNA replication. Implications: This study reveals a previously unrecognized nuclear function for NDRG1 and TGM2 in regulating DNA replication fork stability and recovery and uncovers a stress-responsive mechanism that supports replication homeostasis in cancer cells and advance our understanding of how extracellular signals are integrated with replication and repair pathways.</p>","PeriodicalId":19095,"journal":{"name":"Molecular Cancer Research","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13112271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147581717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Trifecta of Polo-like Kinases, Cancer, and the Immune System: Emerging Intersections and Therapeutic Insights.","authors":"Tanya Jaiswal, Carl A Shirley, Ichwaku Rastogi, Gagan Chhabra, Hao Chang, Nihal Ahmad","doi":"10.1158/1541-7786.MCR-25-1138","DOIUrl":"10.1158/1541-7786.MCR-25-1138","url":null,"abstract":"<p><p>Cancer remains one of the most pressing global health challenges, with immunotherapy being a promising treatment option. However, numerous clinical challenges such as recurrence and resistance persist, underscoring the urgent need for a deeper understanding of the mechanisms that influence immune responses in cancer. Polo-like kinases (PLKs), a family of enzymes with five members, PLK1 through PLK5, have been implicated in cancer progression, and their inhibition is being actively explored for cancer management. While past studies of the PLK family are largely confined to their role in the cell cycle and corresponding chromatin dynamics, recent research has unveiled important connections between PLKs and cancer immunity, particularly in relation to critical signaling pathways such as interferon (IFN) signaling, immunogenic cell death (ICD), TGF-β signaling, and FAS/FASL signaling. While much of the research has focused on PLK1, additional members of the PLK family are beginning to attract attention due to their potential implications in cancer immunity. Understanding the intricate role of PLKs in cancer immunity is an emerging field with tremendous potential. This review offers a comprehensive overview of current knowledge connecting the members of the PLK family with cancer immunology and provides considerations for further research to uncover how PLK signaling can be strategically targeted to optimize cancer immunotherapy to enhance clinical responses.</p>","PeriodicalId":19095,"journal":{"name":"Molecular Cancer Research","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13148149/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147499708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gastric epithelium from BRCA1 and BRCA2 carriers harbors increased double-stranded DNA damage and enhanced growth potential.","authors":"Kole H Buckley, Michaela E Dungan, Kevin Dinh, Gregory M Kelly, Ryan Hausler, Kate E Bennett, Daniel G Clay, Julia E Youngman, Ariana D Majer, Keely A Beyries, Blake A Niccum, Sydney M Shaffer, Tatiana A Karakasheva, Kathryn E Hamilton, Michael L Kochman, Gregory G Ginsberg, Nuzhat Ahmad, Kara N Maxwell, Bryson W Katona","doi":"10.1158/1541-7786.MCR-25-0970","DOIUrl":"10.1158/1541-7786.MCR-25-0970","url":null,"abstract":"<p><p>An accumulating body of evidence suggests carriers of a pathogenic germline variant (PGV) in BRCA1 or BRCA2 have increased gastric cancer (GC) risk. BRCA1 and BRCA2 are tumor suppressor genes involved in promoting homologous recombination to repair double-stranded DNA breaks. The aim of this investigation was to identify differences within the gastric epithelium and in patient-derived gastric organoids (PDGOs) between BRCA1 and BRCA2 carriers and non-carriers to determine if evidence of early gastric carcinogenesis exists amongst these carriers. First, using gastric epithelial biopsies, BRCA2 carriers were found to harbor higher expression of the proliferative marker Ki-67 within the antral gastric epithelium and strikingly, biopsies from both BRCA1 and BRCA2 carriers displayed a marked increase in double-stranded DNA damage. These results were further explored using PDGOs, where a growth advantage was observed for both BRCA1 and BRCA2 PDGOs compared to non-carrier PDGOs. Furthermore, both BRCA1 and BRCA2 PDGOs displayed a more pronounced enhancement of Ki-67 expression as well as increased double stranded DNA damage compared to non-carrier PDGOs. Importantly, none of the PDGOs showed signs of BRCA1 or BRCA2 loss of heterozygosity, potentially indicating a haploinsufficient phenotype. Taken together, these novel findings suggest that haploinsufficiency in BRCA1 and BRCA2 carriers may lead to DNA damage in the gastric epithelium, which may serve as an early event contributing to GC development. Implications: The elevated risk in GC for BRCA1 and BRCA2 PGV carriers may be due to haploinsufficiency and warrants further investigation into BRCA1 and BRCA2-associated GC.</p>","PeriodicalId":19095,"journal":{"name":"Molecular Cancer Research","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13110856/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147499736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of USP7 destabilizes the noncanonical PRC1.1 complex and induces neuroblastoma differentiation.","authors":"Emily A Cmarik, Abhishek Wahi, Sayali S Chandekar, Solomon K Otchere, Jennifer E Sturgis, Silvi Salhotra, Allen T Basanthakumar, Nehemiah X Boyd, Giulia DiGiovanni, He Zhu, Gabriela Alexe, Daniel A Schaefer, Xing Liu, Jarrod A Marto, Sara J Buhrlage, Kimberly Stegmaier, Nathaniel W Mabe","doi":"10.1158/1541-7786.MCR-25-1153","DOIUrl":"10.1158/1541-7786.MCR-25-1153","url":null,"abstract":"<p><p>Pediatric cancers are frequently driven by genomic alterations that result in impaired differentiation during development. To identify complex-level dependencies required for differentiation in neuroblastoma, a pediatric cancer of the developing peripheral nervous system, we curated a list of protein complexes using the CORUM database and mined the Dependency Map (DepMap) using gene set enrichment analysis. This analysis identified the non-canonical PRC1.1 complex, which represses transcriptional activity through ubiquitination of histone 2A, lysine 119 (H2AK119Ub), as a selectively enriched dependency in neuroblastoma. Knockout of PRC1.1 subunits reduced neuroblastoma growth by inducing a neuronal differentiation program. While no known direct inhibitors of PRC1.1 exist, co-dependency analysis identified that the deubiquitinase USP7 strongly correlated with PRC1.1 dependency. Treatment with XL177A, a small molecule inhibitor of USP7, significantly reduced neuroblastoma growth in both cellular and animal models. Integrated RNA- and ChIP-sequencing showed that both PRC1.1 knockout and USP7 inhibition resulted in highly correlated transcriptional alterations and reduced H2AK119Ub deposition on chromatin, suggesting that USP7 inhibition reduced neuroblastoma growth through a PRC1.1-dependent mechanism. Mechanistically, global proteomics and ubiquitinomics revealed that USP7 inhibition disrupted non-canonical PRC1 complex assembly, resulting in destabilization of PRC1.1 and subsequent proteolysis. Our findings expand our understanding of the chromatin complexes required to maintain a de-differentiated state in neuroblastoma and suggest the therapeutic potential for USP7 inhibitors in the treatment of this disease. Implications: Our study reveals the potential for utilizing USP7 inhibitors to target epigenetic repression of differentiation programs in neuroblastoma by reducing PRC1 activity.</p>","PeriodicalId":19095,"journal":{"name":"Molecular Cancer Research","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13082235/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147487062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding the biology of the blood-brain tumor barrier in brain cancer.","authors":"Jorge L Jimenez Macias, Philippa Vaughn-Beaucaire, Jingxu Yan, Jasmine Clark, Sean E Lawler","doi":"10.1158/1541-7786.MCR-25-0908","DOIUrl":"10.1158/1541-7786.MCR-25-0908","url":null,"abstract":"<p><p>Brain cancers are among the most lethal and challenging malignancies to treat in the clinic. An important impediment to effectively treat brain tumors is the blood-brain tumor barrier (BTB), an interface generated between the blood-brain barrier (BBB) and intra-cranial tumors, creating a tumor-permissive perivascular microenvironment. The BTB loses endothelial barrier properties in an heterogeneous manner across the tumor, but continues to impede effective intra-tumoral drug delivery, dramatically decreasing the potential of many anti-neoplastic pharmaceutics. This review will provide a summary of our current understanding of the molecular composition and cellular architecture of the BTB, focusing on glioblastoma and other high-grade gliomas. We will summarize different multi-omic and spatial studies performed with the goal to reveal unknown traits of the brain cancer-associated vasculature and identify molecular targets of therapeutic relevance. Our work aims to consolidate our current understanding of the vasculature in brain tumors, and the insights held regarding its role in brain cancer biology and therapeutic drug delivery.</p>","PeriodicalId":19095,"journal":{"name":"Molecular Cancer Research","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147487031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}