Molecular Oncology最新文献_第2页

Tumor mutational burden as a determinant of metastatic dissemination patterns. 肿瘤突变负荷作为转移传播模式的决定因素。

IF 4.5 2区医学

Molecular Oncology Pub Date : 2026-05-01 Epub Date: 2026-01-27 DOI: 10.1002/1878-0261.70200

Eduardo Candeal, Andrea Moreno-Manuel, Miguel Salvadó-Pertierra, Cristina Santos-Vivas, Rebeca Sanz-Pamplona

{"title":"Tumor mutational burden as a determinant of metastatic dissemination patterns.","authors":"Eduardo Candeal, Andrea Moreno-Manuel, Miguel Salvadó-Pertierra, Cristina Santos-Vivas, Rebeca Sanz-Pamplona","doi":"10.1002/1878-0261.70200","DOIUrl":"10.1002/1878-0261.70200","url":null,"abstract":"According to the seed and soil hypothesis, the organ specificity of metastasis is not a random process and depends on multiple tumor-intrinsic and microenvironmental factors. In this study, we characterized the mutational landscape of a large cohort of human metastatic samples to investigate whether mutational trends determine metastatic dissemination. Genomic data from nine cancer types (bladder, breast, colorectal, endometrial, melanoma, non-small cell lung cancer, ovarian, pancreatic, and prostate) including 19827 patients were obtained from a pan-cancer study. When restricting the analysis to driver mutations, no robust, recurrent mutational patterns associated with metastatic locations were identified across cancer types. However, when cancer types were analyzed separately, mutational trends associated with specific metastatic locations emerged. Considering the total tumor mutational burden (TMB), central nervous system (CNS)/brain and lung metastases harbored a higher TMB than other metastatic locations. Since higher TMB in CNS/brain metastases was also associated with improved prognosis, these findings may be pivotal in refining immunotherapy strategies. Indeed, this observation was confirmed in an independent dataset including patients treated with immunotherapy. In conclusion, our findings suggest that TMB may have greater influence on metastatic organotropism than driver mutational background.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"1364-1378"},"PeriodicalIF":4.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146053049","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}

引用次数: 0

Basroparib inhibits YAP-driven cancers by stabilizing angiomotin. Basroparib通过稳定血管运动素抑制yap驱动的癌症。

IF 4.5 2区医学

Molecular Oncology Pub Date : 2026-05-01 Epub Date: 2026-01-22 DOI: 10.1002/1878-0261.70209

Young-Ju Kwon, Dong Young Kim, Yuna Kim, Uk-Il Kim, Jae-Sung Kim

{"title":"Basroparib inhibits YAP-driven cancers by stabilizing angiomotin.","authors":"Young-Ju Kwon, Dong Young Kim, Yuna Kim, Uk-Il Kim, Jae-Sung Kim","doi":"10.1002/1878-0261.70209","DOIUrl":"10.1002/1878-0261.70209","url":null,"abstract":"Yes-associated protein (YAP) is a key oncogenic effector and a well-established driver of resistance to anticancer therapies, especially in tumors harboring KRAS mutations. Although YAP is clinically relevant, drug-development efforts that directly inhibit its activity have been limited. Here, we show that basroparib-a selective tankyrase (TNKS) inhibitor that suppresses Wnt signaling-attenuates YAP-driven oncogenic programs by stabilizing angiomotin (AMOT), an endogenous negative regulator of YAP. In colorectal cancer (CRC) cells, basroparib increased AMOT protein abundance, promoted AMOT-YAP complex formation, and enforced cytoplasmic sequestration of YAP, thereby dampening YAP-dependent transcription. Basroparib preferentially sensitized YAP-overexpressing, KRAS-mutant CRC cell lines to MEK inhibition by inhibiting YAP signaling. In MEK inhibitor-resistant CRC models, in which elevated YAP activity mediates escape, basroparib restored drug sensitivity both in vitro and in vivo. The compound also enhanced MEK inhibitor efficacy in other YAP-active tumor types, while exerting minimal effects in YAP-inactive models. Taken together, these results identify basroparib-now progressing through clinical development (Phase I, NCT04505839)-as a promising agent for dual Wnt-YAP pathway blockade and for overcoming therapeutic resistance in YAP-driven cancers.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"1284-1298"},"PeriodicalIF":4.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146018979","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}

引用次数: 0

Cell surface interactome analysis identifies TSPAN4 as a negative regulator of PD-L1 in melanoma. 细胞表面相互作用组分析确定TSPAN4是黑色素瘤中PD-L1的负调节因子。

IF 4.5 2区医学

Molecular Oncology Pub Date : 2026-05-01 Epub Date: 2026-01-12 DOI: 10.1002/1878-0261.70182

Guus A Franken, Andrea Abel Gutierrez, Imke van Rossum, Cornelia G Spruijt, Michiel Vermeulen, Guido van Mierlo, Blanca Scheijen, Annemiek B van Spriel

{"title":"Cell surface interactome analysis identifies TSPAN4 as a negative regulator of PD-L1 in melanoma.","authors":"Guus A Franken, Andrea Abel Gutierrez, Imke van Rossum, Cornelia G Spruijt, Michiel Vermeulen, Guido van Mierlo, Blanca Scheijen, Annemiek B van Spriel","doi":"10.1002/1878-0261.70182","DOIUrl":"10.1002/1878-0261.70182","url":null,"abstract":"PD-L1 is a key immune checkpoint ligand that suppresses antitumor immunity by engaging PD-1 on T cells. While therapeutic blockade of PD-L1/PD-1 interactions has shown clinical benefit, many patients fail to respond, indicating modulation by other factors. Here, we identified a novel regulatory axis in which the membrane-organizing protein tetraspanin-4 (TSPAN4) modulates PD-L1 in melanoma cells. Using cell surface proximity biotinylation coupled with mass spectrometry, we discovered that TSPAN4 physically associates with PD-L1, with both proteins colocalizing on migrasomes and retraction fibers. Mechanistically, we show that TSPAN4 negatively regulates PD-L1 protein levels by enhancing its degradation and restricting its lateral mobility at the plasma membrane. Loss of TSPAN4 stabilized PD-L1, promoted its interaction with CMTM6, and increased PD-L1 surface availability for PD-1 binding. Functionally, TSPAN4 knockdown in melanoma cells led to more efficient immune checkpoint blockade through PD-1 on T cells. This study identifies TSPAN4 as a negative regulator of PD-L1 at the cell surface of melanoma cells suggesting that targeting TSPAN4 may offer a new therapeutic strategy to enhance immune checkpoint blockade in melanoma and other cancers.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"1140-1160"},"PeriodicalIF":4.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145959837","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}

引用次数: 0

Crucial parameters for precise copy number variation detection in formalin-fixed paraffin-embedded solid cancer samples. 福尔马林固定石蜡包埋实体癌样品拷贝数变异精确检测的关键参数。

IF 4.5 2区医学

Molecular Oncology Pub Date : 2026-05-01 Epub Date: 2025-12-23 DOI: 10.1002/1878-0261.70192

Hanne Goris, Vasiliki Siozopoulou, Léon C van Kempen, Anne Sieben, Ella Roelant, Stig Hellemans, Elyne Backx, Laure Sorber, Koen De Winne, Senada Koljenović, Karen Zwaenepoel

{"title":"Crucial parameters for precise copy number variation detection in formalin-fixed paraffin-embedded solid cancer samples.","authors":"Hanne Goris, Vasiliki Siozopoulou, Léon C van Kempen, Anne Sieben, Ella Roelant, Stig Hellemans, Elyne Backx, Laure Sorber, Koen De Winne, Senada Koljenović, Karen Zwaenepoel","doi":"10.1002/1878-0261.70192","DOIUrl":"10.1002/1878-0261.70192","url":null,"abstract":"Copy number variations (CNVs) play a crucial role in cancer diagnostics and prognostics, potentially impacting treatment decisions. Ultra-low-pass whole-genome sequencing (ULP-WGS) has emerged as a promising alternative to array-based methods for CNV detection, especially in formalin-fixed paraffin-embedded (FFPE) samples. However, sequencing biases and sample heterogeneity necessitate the optimization of CNV detection tools for FFPE sample-derived data. This study evaluates three open-source CNV callers (CNVpytor, ichorCNA, and WisecondorX) using ULP-WGS and compares their performance against a single nucleotide polymorphism (SNP) array. Our results demonstrate that under optimal experimental conditions, ichorCNA and WisecondorX achieved equal detection of true positive results, with reduced false positive results compared to the SNP array. The SNP array detection pattern differed somewhat from that of the CNV callers, while ichorCNA and WisecondorX had the most comparable detection pattern. We highlight the importance of (pre-)analytical parameters such as neoplastic cell content, sequencing coverage, and bin size selection on CNV detection accuracy. Our findings support the adoption of ULP-WGS-based CNV detection as a robust alternative to SNP arrays, with WisecondorX emerging as the most suitable tool for clinical implementation.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"1270-1283"},"PeriodicalIF":4.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145820236","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}

引用次数: 0

LDAcoop: Integrating non-linear population dynamics into the analysis of clonogenic growth in vitro. 将非线性种群动力学整合到体外克隆生长分析中。

IF 4.5 2区医学

Molecular Oncology Pub Date : 2026-05-01 Epub Date: 2025-12-26 DOI: 10.1002/1878-0261.70185

Nikko Brix, Daniel Samaga, Katharina Gehr, Benedek Dankó, Mohamed Schumann, Guido Drexler, Ahmed Alnatsha, Georg Beyer, Ujjwal Mahajan, Martin Selmansberger, Julia Mayerle, Claus Belka, Horst Zitzelsberger, Kirsten Lauber

{"title":"LDAcoop: Integrating non-linear population dynamics into the analysis of clonogenic growth in vitro.","authors":"Nikko Brix, Daniel Samaga, Katharina Gehr, Benedek Dankó, Mohamed Schumann, Guido Drexler, Ahmed Alnatsha, Georg Beyer, Ujjwal Mahajan, Martin Selmansberger, Julia Mayerle, Claus Belka, Horst Zitzelsberger, Kirsten Lauber","doi":"10.1002/1878-0261.70185","DOIUrl":"10.1002/1878-0261.70185","url":null,"abstract":"The limiting dilution assay (LDA) is a key method to quantify clonogenic cells with self-renewing capacity in vitro, crucial for preclinical cancer research and therapy response assessment. It estimates the frequency of individual clonogenic, stem-like cells within a population based on their ability to form colonies with ≥50 cells at limiting cell numbers. Standard LDA analysis relies on linear, single-hit Poisson models, yet clonogenic growth under single-cell conditions often involves cooperative or competitive dynamics, violating this linearity assumption. Here, we present a modeling framework incorporating non-linear population dynamics into LDA analysis and introduce LDAcoop, an R-based tool for universal quantification of clonogenic cells in LDA formats. Across multiple cancer cell types, we benchmarked LDA against the colony formation assay (CFA) and show that LDA outperforms CFA, especially for patient-derived organoids, suspension cultures, and higher throughput applications. This renders the LDA format particularly suitable for larger-scale pharmacogenomic screening and drug sensitivity testing in complex models. Our results establish LDA and LDAcoop as versatile, scalable tools for robust quantification of clonogenic growth, supporting preclinical drug development and molecular precision oncology research.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"1237-1252"},"PeriodicalIF":4.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145843850","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}

引用次数: 0

Revisiting Mission-Oriented Cancer Research to tackle the increasing burden of cancer in Europe-a policy perspective. 重新审视使命导向的癌症研究，以解决欧洲日益增加的癌症负担——政策视角。

IF 4.5 2区医学

Molecular Oncology Pub Date : 2026-05-01 Epub Date: 2026-04-10 DOI: 10.1002/1878-0261.70249

Manuel Heitor, Julio Celis, Ulrik Ringborg

{"title":"Revisiting Mission-Oriented Cancer Research to tackle the increasing burden of cancer in Europe-a policy perspective.","authors":"Manuel Heitor, Julio Celis, Ulrik Ringborg","doi":"10.1002/1878-0261.70249","DOIUrl":"10.1002/1878-0261.70249","url":null,"abstract":"Cancer as the second leading cause of death in Europe poses an escalating challenge that needs urgent action. Translational cancer research should be the primary focus for addressing the increasing cancer burden in Europe and counteracting the present main strategy to convert cancer to a chronic disease. From a policy perspective, the translational cancer research continuum should be strengthened. The EU Mission on Cancer (MoC), alongside Europe's Beating Cancer Plan (EBCP), should be revisited to prioritize prevention, early detection, and improved treatment with a focus on increasing cure rates and enhancing patients' quality of life, especially for those with incurable disease. The MoC should be strengthened through long-term, sustainable funding of competitively selected Comprehensive Cancer Centers (CCCs) integrating cancer care, health care dependent prevention, research, and education across Europe to ensure stewardship by problem owners. This is critical to avoid the traditional, fragmented \"short-term, project-based funding\" structure of the European Commission's collaborative research, which relies on many small projects dispersed across varied institutional contexts. Articulation with frontier research in Europe, supported by the European Research Council (ERC), and with critical innovations, including those sponsored by the European Innovation Council (EIC), becomes paramount. The current goal to establish around 100 CCCs is highly commendable, with each CCC and related networks targeting between 3.5 and 4 million people, following adequate accreditation procedures. In addition, the political ownership of the MoC should ensure adequate coordination/integration with the EBCP, together with appropriate engagement and responsibility on the part of national and European authorities to address policy and implementation actions. In summary, our policy analysis recommends establishing a coherent cancer research continuum to drive therapeutic innovation and strengthen prevention.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"1098-1110"},"PeriodicalIF":4.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147645823","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}

引用次数: 0

Correlation of the differential expression of PIK3R1 and its spliced variant, p55α, in pan-cancer. PIK3R1及其剪接变体p55α在泛癌中差异表达的相关性

IF 4.5 2区医学

Molecular Oncology Pub Date : 2026-05-01 Epub Date: 2026-01-20 DOI: 10.1002/1878-0261.70205

Ishita Gupta, Yang Song, Madeleine Ndahayo, Anirudh Saxena, Theresa Guo, Dylan Z Kelley, Jessica Gore, Andrew Hennigan, Alexa Anderson, John C Papadimitriou, Daria A Gaykalova

{"title":"Correlation of the differential expression of PIK3R1 and its spliced variant, p55α, in pan-cancer.","authors":"Ishita Gupta, Yang Song, Madeleine Ndahayo, Anirudh Saxena, Theresa Guo, Dylan Z Kelley, Jessica Gore, Andrew Hennigan, Alexa Anderson, John C Papadimitriou, Daria A Gaykalova","doi":"10.1002/1878-0261.70205","DOIUrl":"10.1002/1878-0261.70205","url":null,"abstract":"PIK3R1, a regulatory subunit of class IA phosphoinositide-3-kinase (PI3K), undergoes alternative splicing to generate multiple isoforms, primarily p85α and p55α. The canonical isoform p85α associates with the catalytic subunit p110α to form the active PI3K complex, which regulates key cellular functions such as growth, proliferation, survival, and metabolism. In this study, we performed a comprehensive pan-cancer analysis integrating transcriptomic, proteomic, and genomic data to investigate the expression patterns of p85α and its splicing variant, p55α, and their associations with clinical outcomes. Our findings reveal that while p85α expression is significantly reduced, p55α is elevated in tumors as compared to normal samples. These alterations are linked to poor prognosis across multiple cancer types. Notably, we observed racial disparities in expression patterns, with African American patients exhibiting more pronounced downregulation of p85α and upregulation of p55α than European Americans, potentially contributing to differential clinical outcomes. This is the first study to systematically evaluate p85α and p55α expression across diverse cancers and populations, highlighting the role of alternative splicing in PI3K pathway dysregulation and its relevance to cancer progression and health disparities.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"1299-1322"},"PeriodicalIF":4.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146003747","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}

引用次数: 0

The neural crest-associated gene ERRFI1 is involved in melanoma progression and resistance toward targeted therapy. 神经嵴相关基因ERRFI1参与黑色素瘤的进展和对靶向治疗的耐药性。

IF 4.5 2区医学

Molecular Oncology Pub Date : 2026-05-01 Epub Date: 2025-10-03 DOI: 10.1002/1878-0261.70137

Nina Wang, Qian Sun, Daniel Novak, Lei Zhu, Juliane Poelchen, Tamara Steinfass, Yiman Wang, Viktor Umansky, Jochen Utikal

{"title":"The neural crest-associated gene ERRFI1 is involved in melanoma progression and resistance toward targeted therapy.","authors":"Nina Wang, Qian Sun, Daniel Novak, Lei Zhu, Juliane Poelchen, Tamara Steinfass, Yiman Wang, Viktor Umansky, Jochen Utikal","doi":"10.1002/1878-0261.70137","DOIUrl":"10.1002/1878-0261.70137","url":null,"abstract":"Targeted therapy has been established as a therapeutic option for the treatment of metastatic melanoma. Despite initially being very efficient, many tumors develop resistance to targeted therapy, leading to its failure. We previously demonstrated that the neural crest (NC)-associated gene ERRFI1 is highly expressed in metastatic melanoma and correlates with a bad prognosis. Here, we show that the expression of ERRFI1 was upregulated in melanoma and negatively correlated with the expression of melanocytic differentiation markers, such as MITF and TYR. Downregulation of ERRFI1 with the help of siRNA increased the susceptibility of melanoma cells toward BRAF inhibition (BRAFi) and resensitized BRAFi-resistant melanoma cells to BRAFi. Mass spectrometry-based proteomic analysis revealed that ERRFI1 silencing diminished the activation of the mitogen-activated protein kinase (MAPK) and AKT signaling pathways, which usually contribute to drug resistance. Furthermore, we show that miR-200c targeted the 3'UTR of ERRFI1 and reduced its expression, resulting in the resensitization of BRAFi-resistant melanoma cells to BRAFi. Our study results suggest that ERRFI1 could be a potential therapeutic target for the treatment of metastatic melanoma.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"1185-1201"},"PeriodicalIF":4.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225478","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}

引用次数: 0

Recurrent cancer-associated ERBB4 mutations are transforming and confer resistance to targeted therapies. 复发性癌症相关ERBB4突变正在转化并赋予对靶向治疗的抗性。

IF 4.5 2区医学

Molecular Oncology Pub Date : 2026-05-01 Epub Date: 2025-12-23 DOI: 10.1002/1878-0261.70189

Veera K Ojala, Sini Ahonen, Sara Peltola, Aura Tuohisto-Kokko, Olaya Esparta, Peppi Suominen, Anne Jokilammi, Iman Farahani, Deepankar Chakroborty, Nikol Dibus, Steffen Boettcher, Tomi T Airenne, Mark S Johnson, Lisa D Eli, Klaus Elenius, Kari J Kurppa

{"title":"Recurrent cancer-associated ERBB4 mutations are transforming and confer resistance to targeted therapies.","authors":"Veera K Ojala, Sini Ahonen, Sara Peltola, Aura Tuohisto-Kokko, Olaya Esparta, Peppi Suominen, Anne Jokilammi, Iman Farahani, Deepankar Chakroborty, Nikol Dibus, Steffen Boettcher, Tomi T Airenne, Mark S Johnson, Lisa D Eli, Klaus Elenius, Kari J Kurppa","doi":"10.1002/1878-0261.70189","DOIUrl":"10.1002/1878-0261.70189","url":null,"abstract":"Receptor tyrosine kinase ERBB4 (HER4) is frequently mutated in human cancer, and ERBB4 mutations have been identified in patients relapsing on targeted therapy. Here, we addressed the functional consequences of recurrent cancer-associated ERBB4 mutations that are located at regions important for receptor activation and/or are paralogous to known oncogenic hotspot mutations in other ERBB genes. Eleven out of 18 analyzed mutations were transforming in cell models, thus suggesting oncogenic potential for more than half of the recurrent ERBB4 mutations. More detailed analyses of the most potent mutations, S303F, E452K, and L798R, showed that they are activating, can co-operate with other ERBB receptors and are sensitive to clinically available second-generation pan-ERBB inhibitors neratinib, afatinib, and dacomitinib. Furthermore, the S303F mutation, together with a previously identified activating ERBB4 mutation, E715K, promoted resistance to third-generation EGFR inhibitor osimertinib in EGFR-mutant lung cancer model in vitro and in vivo. Together, these results are expected to facilitate clinical interpretation of the most recurrent cancer-associated ERBB4 mutations. The findings provide rationale for testing the efficacy of clinically used pan-ERBB inhibitors in patients harboring driver ERBB4 mutations both in the treatment-naïve setting, and upon development of resistance to targeted agents.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"1323-1346"},"PeriodicalIF":4.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145820197","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}

引用次数: 0

Correction to "Ectopic expression of cancer/testis antigen SSX2 induces DNA damage and promotes genomic instability". 更正“癌/睾丸抗原SSX2异位表达诱导DNA损伤并促进基因组不稳定”。

IF 4.5 2区医学

Molecular Oncology Pub Date : 2026-05-01 Epub Date: 2026-04-27 DOI: 10.1002/1878-0261.70253

引用次数: 0