Molecular Oncology最新文献

{"title":"Multiplex single-cell profiling of putative cancer stem cell markers ALDH1, SOX9, SOX2, CD44, CD133 and CD15 in endometrial cancer.","authors":"Hilde E Lien, Marta E Hjelmeland, Hege F Berg, Rose M Gold, Kathrine Woie, Lars A Akslen, Ingfrid S Haldorsen, Camilla Krakstad","doi":"10.1002/1878-0261.13815","DOIUrl":"10.1002/1878-0261.13815","url":null,"abstract":"<p><p>The presence of cancer stem cells is linked to aggressive disease and higher risk of recurrence, and multiple markers have been proposed to detect cancer stem cells. However, a detailed evaluation of the expression patterns and the prognostic value of markers relevant for endometrial cancer is lacking. As organoid models are suggested to be enriched in cancer stem cells, such models may prove valuable to define tissue-specific cancer stem cells. To address this, imaging mass cytometry and multiplex single-cell analyses were performed on an endometrial cancer patient series including both tumor biopsies and corresponding patient-derived organoids. An antibody panel focused on cancer stem cell markers was used to identify cancer stem cell phenotypes. Over 70% of epithelial cells in the tumor biopsies expressed at least one putative cancer stem cell marker. We identified distinct cancer cell phenotypes with heterogeneous expression within individual patients and between patient samples. Few differences in the distribution of cancer cell phenotypes were observed between tumor biopsies and corresponding organoids. Cells expressing aldehyde dehydrogenase 1 (ALDH1) were more prevalent in high-grade tumors, while expression of CD44 was more prevalent in grade 1 tumors. Spatial analysis revealed significantly less interaction between ALDH1- and CD44-expressing cells. Gene expression data was used to further investigate selected markers. CD44 gene expression was associated with a favorable prognosis and was further validated using immunohistochemistry. High expression of CD44 was significantly associated with better survival. The general high expression of proposed stem cell markers may indicate alternative roles for these in endometrial cancer.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"1651-1667"},"PeriodicalIF":6.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12161474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066758","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":"Stochastic variation in the FOXM1 transcription program mediates replication stress tolerance.","authors":"Hendrika A Segeren, Kathryn A Wierenga, Frank M Riemers, Elsbeth A van Liere, Bart Westendorp","doi":"10.1002/1878-0261.13819","DOIUrl":"10.1002/1878-0261.13819","url":null,"abstract":"<p><p>Oncogene-induced replication stress (RS) is a vulnerability of cancer cells that forces reliance on the intra-S-phase checkpoint to ensure faithful genome duplication. Inhibitors of the intra-S-phase checkpoint kinases ATR and CHK1 have been developed, but resistance to these drugs remains problematic. Understanding drug tolerance mechanisms is impeded by analysis of bulk samples, which neglect tumor heterogeneity and often fail to accurately interpret cell cycle-mediated resistance. Here, by combining intracellular immunostaining and single-cell RNA-sequencing, we characterized the transcriptomes of oncogenic RAS-expressing cells with variable levels of RS when challenged with a CHK1 inhibitor combined with gemcitabine. We identified 37 genes differentially expressed between tolerant and sensitive cells, including several FOXM1 targets. While complete knockdown of FOXM1 impeded cell proliferation, partial knockdown protected cells against DNA damage, and improved recovery from drug-induced RS. Remarkably, knockdown of individual FOXM1 target genes UBE2C and MKI67 also mitigated DNA damage, uncovering unanticipated roles for these in the replication stress response. Our results suggest that low levels of FOXM1-dependent gene expression during S and G2 phase protects cells against excessive DNA damage during drug-induced replication stress.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"1633-1650"},"PeriodicalIF":6.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12161472/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143516196","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":"Crosstalk between gut microbiota and tumor: tumors could cause gut dysbiosis and metabolic imbalance.","authors":"Siyuan Zhang, Haimei Wen, Ying Chen, Jingya Ning, Di Hu, Yujiao Dong, Chenyu Yao, Bo Yuan, Shuanying Yang","doi":"10.1002/1878-0261.13763","DOIUrl":"10.1002/1878-0261.13763","url":null,"abstract":"<p><p>Gut microbiota has a proven link with the development and treatment of cancer. However, the causality between gut microbiota and cancer development is still unknown and deserves exploration. In this study, we aimed to explore the alterations in gut microbiota in murine tumor models and the crosstalk between the tumor and the gut microbiota. The subcutaneous and intravenous murine tumor models using both the colorectal cancer cell line MC38 and lung cancer cell line LLC were constructed. Then fecal samples before and after tumor inoculation were collected for whole metagenomics sequencing. Both subcutaneous and metastatic tumors markedly elevated the α-diversity of the gut microbiota. Relative abundance of Ligilactobacillus and Lactobacillus was reduced after subcutaneously inoculating tumor cells, whereas Bacteroides and Duncaniella were reduced in metastatic tumors, regardless of tumor type. At the species level, Lachnospiraceae bacterium was enriched after both subcutaneous and intravenous tumors inoculation, whereas levels of Muribaculaceae bacterium Isolate-110 (HZI), Ligilactobacillus murinus and Bacteroides acidifaciens reduced. Metabolic function analysis showed that the reductive pentose phosphate cycle, urea cycle, ketone body biosynthesis, ectoine biosynthesis, C4-dicarboxylic acid cycle, isoleucine biosynthesis, inosine 5'-monophosphate (IMP), and uridine 5'-monophosphate (UMP) biosynthesis were elevated after tumor inoculation, whereas the cofactor and vitamin biosynthesis were deficient. Principal coordinates analysis (PCoA) showed that subcutaneous and metastatic tumors partially shared the same effect patterns on gut microbiota. Furthermore, fecal microbiota transplantation revealed that this altered microbiota could influence tumor growth. Taken together, this study demonstrated that both colorectal cancer (MC38) and non-colorectal cancer (LLC) can cause gut dysbiosis and metabolic imbalance, regardless of tumor type and process of tumor inoculation, and this dysbiosis influenced the tumor growth. This research gives novel insights into the crosstalk between tumors and the gut microbiota.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"1707-1724"},"PeriodicalIF":6.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12161466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142730721","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":"EACR 2025 Congress: Innovative Cancer Science, 16-19 June 2025.","authors":"","doi":"10.1002/1878-0261.70070","DOIUrl":"10.1002/1878-0261.70070","url":null,"abstract":"<p><p>Abstracts submitted to the 'EACR 2025 Congress: Innovative Cancer Science', from 16-19 June 2025 and accepted by the Congress Organising Committee are published in this Supplement of Molecular Oncology, an affiliated journal of the European Association for Cancer Research (EACR).</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":"19 Suppl 1 ","pages":"1-895"},"PeriodicalIF":6.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12155586/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275421","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":"Dose-dependent induction of epithelial-mesenchymal transition in 3D melanoma models by non-thermal plasma treatment.","authors":"Eline Biscop, Edgar Cardenas De La Hoz, Hanne Verswyvel, Joey De Backer, Ho Wa Lau, Angela Privat-Maldonado, Wim Vanden Berghe, Steve Vanlanduit, Evelien Smits, Annemie Bogaerts, Abraham Lin","doi":"10.1002/1878-0261.70055","DOIUrl":"https://doi.org/10.1002/1878-0261.70055","url":null,"abstract":"<p><p>Despite the promising results of non-thermal plasma (NTP) devices for cancer therapy, the potential adverse effects of NTP irradiation have remained unexplored, including the effects on epithelial-mesenchymal transition (EMT) and subsequent cancer metastasis. In this study, we investigate NTP-induced EMT initiation and progression. A microsecond-pulsed dielectric barrier discharge plasma device was used for NTP treatment, and chicken chorioallantoic membrane (CAM) and spheroids were used as 3D tumor models. NTP treatment reduced tumor volume in the CAM model, but a shift towards a mesenchymal-like phenotype was also measured in melanoma tumors via analysis of the six EMT biomarkers, though changes in cancer cell migration to other organs were not significant. In the spheroid model, molecular analysis also indicated an EMT response following NTP treatment, and enhanced cell migration was measured in one cell line. EMT induction with NTP was dose-dependent and transient; high NTP treatments caused significant EMT response and enhanced migration, but low NTP doses did not. Our findings highlight the important role of NTP parameters for cancer treatment and consequential EMT responses. The insights obtained here further build the foundation for clinical optimization, harnessing the cancer-killing potential of NTP while safeguarding against undesirable EMT-related outcomes.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144182860","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":"Therapeutic applications of a novel humanized monoclonal antibody targeting chemokine receptor CCR9 in pancreatic cancer.","authors":"Hannah G McDonald, Anna M Reagan, Charles J Bailey, Mei Gao, Muqiang Gao, Angelica L Solomon, Michael J Cavnar, Prakash K Pandalai, Mautin T Barry-Hundeyin, Megan M Harper, Justin A Rueckert, Ángela Turrero, Araceli Tobio, Anxo Vidal, Daniel Roca-Lema, Elia Álvarez-Coiradas, Pablo Garrido, Laureano Simón, Joseph Kim","doi":"10.1002/1878-0261.70062","DOIUrl":"https://doi.org/10.1002/1878-0261.70062","url":null,"abstract":"<p><p>The relative failure of immune checkpoint inhibitors in pancreatic ductal adenocarcinoma (PDAC) despite having a dense, immunosuppressive tumor microenvironment highlights the need to target alternate/escape pathways. We have previously examined C-C chemokine receptor type 9 (CCR9) as a candidate immune checkpoint and developed a targeted, humanized monoclonal antibody (SRB2). Cytotoxicity of SRB2 was evaluated in vitro and in vivo. CCR9 expression on PDAC cells/tissues, immune components of patient-derived organoids (PDOs), and antibody-dependent cell-mediated cytotoxicity were examined. In PANC-1 and MIA PaCa-2 cell lines, we demonstrated highest CCR9 expression; however, no direct cytotoxic effect was observed with SRB2 treatment. In PANC-1 cells, NK cell-mediated cytotoxicity was promoted by SRB2. Dose-dependent SRB2 cytotoxicity was observed in PDAC PDOs. In patient-derived xenograft mouse models, cytotoxicity of SRB2 monotherapy and in combination with oxaliplatin was also shown. In humanized immune-competent mouse models, SRB2 efficacy was similar to other drugs, but two mice in this cohort had complete tumor regression. Our current studies suggest that therapeutic targeting of CCR9 may improve PDAC outcomes, and additional studies are underway to evaluate SRB2 for clinical use.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144174177","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":"BMP antagonist CHRDL2 enhances the cancer stem-cell phenotype and increases chemotherapy resistance in colorectal cancer.","authors":"Eloise Clarkson, Annabelle Lewis","doi":"10.1002/1878-0261.70064","DOIUrl":"https://doi.org/10.1002/1878-0261.70064","url":null,"abstract":"<p><p>Bone morphogenetic protein (BMP) antagonists have been increasingly linked to the development of colorectal cancer (CRC). BMP signalling operates in opposition to the WNT signalling pathway, which sustains stem-cell maintenance and self-renewal of the normal intestinal epithelium. Reduced BMP and elevated WNT signalling lead to expansion of the stem-cell compartment and the hyperproliferation of epithelial cells, a defining characteristic of CRC. Chordin-like-2 (CHRDL2) is a secreted BMP antagonist, with overexpression linked to poor prognosis and variants in the gene shown to be associated with an elevated CRC risk. However, the detailed mechanism by which CHRDL2 contributes to CRC is unknown. In this study, we explored the impact of CHRDL2 overexpression on CRC cells to investigate whether CHRDL2's inhibition of BMP signalling intensifies WNT signalling and enhances the cancer stem-cell phenotype and response to treatment. Our research approach combines 2D cancer cell lines engineered to inducibly overexpress CHRDL2 and 3D organoid models treated with extrinsic CHRDL2, complemented by RNA sequencing analysis. CHRDL2 was found to enhance the survival of organoids and CRC cells during chemotherapy and irradiation treatment due to activation of DNA damage response pathways. Organoids treated with secreted CHRDL2 exhibited elevated levels of stem-cell markers and reduced differentiation, as evidenced by diminished villi budding. RNA-seq analysis revealed that CHRDL2 increased the expression of stem-cell markers, WNT signalling and other well-established cancer-associated pathways through BMP inhibition. These findings collectively suggest that CHRDL2 overexpression could affect response to CRC therapy by enhancing DNA repair and the stem-cell potential of cancer cells, and its role as a biomarker should be further explored.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144174172","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":"Molecular imaging predicts trastuzumab-deruxtecan (T-DXd) response in head and neck cancer xenograft models.","authors":"Abdullah Bin Naveed, Lucas Mani, Muhammad Bilal Mirza, Ashtyn McAdoo, Takahito Kondo, Hidenori Tanaka, Nicole Meeks, Eben Rosenthal, Marisa Hom","doi":"10.1002/1878-0261.70056","DOIUrl":"https://doi.org/10.1002/1878-0261.70056","url":null,"abstract":"<p><p>Erb-b2 receptor tyrosine kinase 2 (ERBB2; also known as HER2) expression is observed in 25-40% of head and neck squamous cell carcinomas (HNSCC), yet there are no anti-HER2 therapies under evaluation for HNSCC, as conventional cytostatic anti-HER2 antibodies have had limited effectiveness and levels of HER2 overexpression are lower in HNSCC tumors compared to breast cancer. Trastuzumab-deruxtecan (T-DXd; Enhertu) is a HER2-targeting antibody-drug conjugate (ADC) comprising an anti-HER2 monoclonal antibody, a cleavable linker, and a potent topoisomerase I inhibitor payload, and has shown promising results in very low HER2-expressing tumors. We compare the efficacy of T-DXd, trastuzumab-emtansine (ADC comprising an anti-HER2 antibody and microtubule inhibitor, T-DM1; Kadcyla) and trastuzumab (Herceptin) therapy in HNSCC with low and absent HER2 expression in vitro and in vivo. In vitro treatment of a low HER2-expressing human HNSCC cell line (FaDu) with T-DXd resulted in dose-dependent cell death (IC50 values of 9856 ng·mL^-1). T-DXd treatment of FaDu and UMSCC-47 (low HER2-expressing cell line) mouse xenografts displayed antitumor activity (P = 0.0001 and 0.015 respectively). When comparing T-DXd to other approved anti-HER2 therapies, only FaDu mice treated with T-DXd showed a reduction in tumor growth (P = 0.0012). In UMSCC-1 cells (absent HER2 expression), the drug failed to accumulate in tumors and showed no measurable antitumor effect, in contrast to FaDu xenografts, where drug accumulation in the tumor correlated with a therapeutic response. T-DXd treatment yielded antitumor activity in FaDu and UMSCC-47 tumors, highlighting the potential for T-DXd efficacy in low HER2-expressing tumors.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144174176","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":"Circulating tumor DNA monitoring and blood tumor mutational burden in patients with metastatic solid tumors treated with atezolizumab.","authors":"Charles Swanton, Russell W Madison, Candice Francheska B Tambaoan, Funda Meric-Bernstam, Christopher J Sweeney, Razelle Kurzrock, Howard A Burris, David R Spigel, Hanna Tukachinsky, Jason Hughes, Julia Malato, Bongin Yoo, Tania Szado, Cheryl Schwab, Lincoln W Pasquina, Amaya Gasco, Katja Schulze, Claire F Friedman","doi":"10.1002/1878-0261.70054","DOIUrl":"https://doi.org/10.1002/1878-0261.70054","url":null,"abstract":"<p><p>Immune checkpoint inhibitors are important for treatment across tumor types but are not universally effective in controlling disease. Early understanding of tumor response, or lack thereof, can inform treatment decisions. This study evaluates changes in circulating tumor DNA (ctDNA) and blood tumor mutational burden (bTMB) for associations with response to programmed cell death 1 ligand 1 (PD-L1) blockade. We sequenced cell-free DNA collected at the start of therapy, on treatment, and at the end of therapy for 153 patients treated with atezolizumab as part of the pan-tumor MyPathway study (NCT02091141). ctDNA tumor fraction (TF) and bTMB were assessed for correlation with progression-free survival (PFS) and overall survival (OS). We found that molecular response (MR, ≥50% decrease in TF at cycle 3 day 1) was associated with improved PFS (9.7 vs 1.5 months from C3D1; HR = 0.27) and OS (21.1 vs 14.3 months from C3D1; HR = 0.44). These findings were consistent when limited to patients with stable disease (SD; PFS HR = 0.55; OS HR = 0.39). bTMB was correlated with tissue-based TMB (tTMB) when TF was high (≥1%), but not with OS in this cohort. In total, 61% of baseline samples had predicted clonal hematopoiesis (CH) variants. No correlation between maximum variant allele frequency (maxVAF) of predicted CH and TF was seen. In summary, MR is associated with outcomes for patients treated with atezolizumab and could stratify patients with SD. While CH was common, maxVAF for CH variants was not associated with ctDNA TF. Quantification of ctDNA enables therapy response monitoring and is critical for interpretation of bTMB as a proxy for tTMB.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144174175","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":"Genomics-led approach to drug testing in models of undifferentiated pleomorphic sarcoma.","authors":"Piotr J Manasterski, Molly R Danks, John P Thomson, Morwenna Muir, Martin Lee, John C Dawson, Ana T Amaral, Juan Diaz-Martin, David S Moura, Javier Martin-Broto, Ali Alsaadi, Donald M Salter, Ailsa J Oswald, Graeme Grimes, Larry Hayward, Ted R Hupp, Karen Sisley, Paul H Huang, Neil O Carragher, Valerie G Brunton","doi":"10.1002/1878-0261.70059","DOIUrl":"https://doi.org/10.1002/1878-0261.70059","url":null,"abstract":"<p><p>Undifferentiated pleomorphic sarcoma (UPS) is a rare cancer with limited systemic treatment options and poor outcomes. To seek novel therapeutic interventions, we undertook mutational analysis of 20 UPS patient tumours, four established UPS cell lines and three patient-derived xenograft (PDX) models. Frequently mutated genes were uncommon; in contrast, copy number (CN) events were common with CN gain frequently observed at genes including JUN, EGFR and CDK6 and loss at WNT8B, RB1 and PTEN. Analysis of overlapping genomic changes between patient tumours and PDX models or cell lines revealed druggable events. A selected panel of drugs targeting these was analysed in in vitro UPS models demonstrating that the mitogen-activated protein kinase kinase (MEK) inhibitor trametinib is synergistic in combination with the fibroblast growth factor receptor (FGFR) inhibitor infigratinib. This was further confirmed to be efficacious in an ex vivo tumour slice model. Taken together, our results demonstrate the rationale for utilising genomic data to identify drug classes targeting druggable events in low-prevalence cancers and indicate that trametinib alone or in combination with infigratinib should be further explored for clinical UPS management.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144143107","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}