Molecular Oncology最新文献_第4页

The VHL tumor suppressor at the crossroad of protein folding, aggregation, and cancer. VHL肿瘤抑制因子在蛋白质折叠、聚集和癌症的十字路口。

IF 4.5 2区医学

Molecular Oncology Pub Date : 2026-09-07 DOI: 10.1002/1878-0261.70325

Lara Abad, Silvio Carlo Ermanno Tosatto, Emanuela Leonardi

引用次数: 0

Profiling neoadjuvant therapy response in rectal cancer using meta-analysis of publicly available transcriptomic RNA-seq datasets. 利用公开可用的转录组RNA-seq数据集的荟萃分析来分析直肠癌新辅助治疗的反应。

IF 4.5 2区医学

Molecular Oncology Pub Date : 2026-09-07 DOI: 10.1002/1878-0261.70324

Aleksandra Stanojevic, Rafael Stroggilos, Mladen Marinkovic, Ana Djuric, Suzana Stojanovic-Rundic, Radmila Jankovic, Sergi Castellvi-Bel, Remond J A Fijneman, Antonia Vlahou, Jerome Zoidakis, Milena Cavic

{"title":"Profiling neoadjuvant therapy response in rectal cancer using meta-analysis of publicly available transcriptomic RNA-seq datasets.","authors":"Aleksandra Stanojevic, Rafael Stroggilos, Mladen Marinkovic, Ana Djuric, Suzana Stojanovic-Rundic, Radmila Jankovic, Sergi Castellvi-Bel, Remond J A Fijneman, Antonia Vlahou, Jerome Zoidakis, Milena Cavic","doi":"10.1002/1878-0261.70324","DOIUrl":"10.1002/1878-0261.70324","url":null,"abstract":"Neoadjuvant chemoradiotherapy followed by total mesorectal excision is standard for locally advanced rectal cancer, but response varies and current markers are insufficient. This study integrates public bulk RNA-seq data to identify predictive features of response. TRIM54 and PABPC4 were upregulated in the responder group, while ADSS1 and MGAT1 were upregulated in the non-responder group. ARMC2 was identified as a predictive biomarker upregulated in pathological complete response. Responder group showed enrichment of NK cells and CD4+ lymphocytes, while immune precursors were linked to poor outcome. Transcription factor analysis revealed SP1 and NFKB activations in the non-responder group and TCF15 in the responder group. SMAD3 and RDXANK were associated with complete regression, while MYC was dominant in incomplete regression. These findings provide insight into mechanisms underlying therapy response. To our knowledge, this is the first meta-analysis using high-throughput sequencing data, providing a valuable starting point for future rectal cancer research.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13548026/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900965","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}

引用次数: 0

Regulation of the lncRNA NEAT1 by p53-ΔNp63 crosstalk modulates the DNA damage response and therapeutic efficacy in HNSCC. p53-ΔNp63串扰对lncRNA NEAT1的调控可调节HNSCC的DNA损伤反应和治疗效果。

IF 4.5 2区医学

Molecular Oncology Pub Date : 2026-09-07 DOI: 10.1002/1878-0261.70331

Sara De Domenico, Veronica La Banca, Silvia D'Amico, Stefano Scalera, Sara Nicolai, Angelo Peschiaroli

{"title":"Regulation of the lncRNA NEAT1 by p53-ΔNp63 crosstalk modulates the DNA damage response and therapeutic efficacy in HNSCC.","authors":"Sara De Domenico, Veronica La Banca, Silvia D'Amico, Stefano Scalera, Sara Nicolai, Angelo Peschiaroli","doi":"10.1002/1878-0261.70331","DOIUrl":"10.1002/1878-0261.70331","url":null,"abstract":"Head and neck squamous cell carcinomas (HNSCCs) are characterized by recurrent genetic alterations, including the inactivation of the tumor suppressor TP53 gene and dysregulation of the TP63 gene. The TP63 gene encodes multiple isoforms, among which the N-terminal truncated isoform ΔNp63 is fundamental for the integrity of stratified epithelial tissues. We previously demonstrated that ΔNp63 represses the expression of the lncRNA NEAT1. Here, we investigated the functional crosstalk between p53 and ΔNp63 in modulating NEAT1 expression following genotoxic stress. We found that upon genotoxic insults, p53 activation and the concomitant downregulation of ΔNp63 promote NEAT1 transcription. In p53-proficient HNSCC cells, NEAT1 targeting leads to increased DNA damage, highlighting its potential role in maintaining genomic stability and facilitating efficient DNA repair. Importantly, we showed that histone deacetylase inhibitors (HDACis) upregulate NEAT1 expression independently of p53, and NEAT1 silencing enhances HDACis-induced DNA damage. Overall, our findings establish NEAT1 as an early regulator of the DNA damage response in HNSCCs and suggest that combining NEAT1 targeting with HDAC inhibition may potentiate therapeutic efficacy, particularly in TP53-mutant HNSCCs.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13548822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900935","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}

引用次数: 0

Mechanisms and therapeutic opportunities of the ribotoxic stress response in cancer. 癌症中核素毒性应激反应的机制和治疗机会。

IF 4.5 2区医学

Molecular Oncology Pub Date : 2026-09-02 DOI: 10.1002/1878-0261.70323

Anastassiya Kim, Maryam Aslam, Elouise Torruella, Alphons Sony, Asif Rahman, Simira Smith, Columba de la Parra, Moira Sauane

{"title":"Mechanisms and therapeutic opportunities of the ribotoxic stress response in cancer.","authors":"Anastassiya Kim, Maryam Aslam, Elouise Torruella, Alphons Sony, Asif Rahman, Simira Smith, Columba de la Parra, Moira Sauane","doi":"10.1002/1878-0261.70323","DOIUrl":"10.1002/1878-0261.70323","url":null,"abstract":"Various environmental and endogenous stressors, including ultraviolet (UV) radiation, cytotoxins, and dysregulated translation, can induce ribosome stalling and collisions, disrupting protein homeostasis. The ribotoxic stress response (RSR) is a cellular surveillance mechanism that senses translational stress and activates stress signaling via the MAP3 kinase ZAKα and the stress-activated protein kinases (SAPKs) p38 and JNK. This review outlines the molecular mechanisms behind RSR, distinguishes RSR from other translational stress response pathways, such as the well-studied integrated stress response (ISR), discusses the role of RSR in key cellular processes, and presents new evidence linking RSR to cancer biology. We explore how ribotoxic stress is exploited by chemotherapeutic agents and other compounds to induce cancer cell death, and the potential limitations of such therapeutic strategy. Finally, we highlight future considerations for inducing the RSR pathway in cancer, highlighting both therapeutic potential and the challenges in this emerging field.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13536839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148875063","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}

引用次数: 0

Castration-resistant prostate cancer cells are addicted to the high activity of cyclin-dependent kinase 2. 去势抵抗性前列腺癌细胞依赖于高活性的周期蛋白依赖性激酶2。

IF 4.5 2区医学

Molecular Oncology Pub Date : 2026-09-02 DOI: 10.1002/1878-0261.70319

Joyeeta Chatterjee, Alessia Marin, Shivani Yalala, Harri M Itkonen

{"title":"Castration-resistant prostate cancer cells are addicted to the high activity of cyclin-dependent kinase 2.","authors":"Joyeeta Chatterjee, Alessia Marin, Shivani Yalala, Harri M Itkonen","doi":"10.1002/1878-0261.70319","DOIUrl":"10.1002/1878-0261.70319","url":null,"abstract":"Cyclin-dependent kinases (CDK) drive the progression through the cell cycle and thereby form classical targets for cancer therapy. Targeting androgen receptor (AR) is effective against prostate cancer (PC), but frequently leads to development of incurable castration-resistant PC (CRPC). We show that emergence of CRPC is associated with significant upregulation of CDK2 cyclins and downregulation of CDK4/6 cyclins. This rewiring renders CRPC cells dependent on the high CDK2 activity, and CDK2-specific inhibitors efficiently decrease proliferation of PC and CRPC cells. We develop a CDK2 inhibitor-resistant CRPC model and perform a rational compound screen to assess which of the currently used anti-CRPC treatments could augment CDK2 therapy-response. This dual approach revealed that when our CRPC model acquired resistance to CDK2 inhibition, it increased AR signaling, and the combination of CDK2 inhibition with anti-androgens induces synergistic antiproliferative effects on CRPC cells. Importantly, CDK2 inhibitors also show synergistic interaction with cell cycle poisons such as Docetaxel and Cisplatin, and combinatorial effects are also seen with radiotherapy, thereby offering multiple combinations against CRPC. In brief, we propose that CDK2 inhibition provides a rational basis for combinatorial therapy against CRPC.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13536838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148875080","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}

引用次数: 0

Longitudinal genome-wide aneuploidy measurements in circulating cell-free DNA to predict lack of benefit from pembrolizumab in patients with metastatic urothelial cancer. 循环无细胞DNA的纵向全基因组非整倍体测量预测转移性尿路上皮癌患者使用派姆单抗缺乏益处

IF 4.5 2区医学

Molecular Oncology Pub Date : 2026-09-01 Epub Date: 2026-06-16 DOI: 10.1002/1878-0261.70272

Youssra Salhi, Stavros Makrodimitris, Sandra van Wilpe, Iris Te Paske, Vanja de Weerd, Corine M Beaufort, Hans M Westgeest, Jens Voortman, Maureen J B Aarts, Maud Rijnders, Astrid A M van der Veldt, Ronald de Wit, Niven Mehra, Saskia M Wilting, Debbie G J Robbrecht

{"title":"Longitudinal genome-wide aneuploidy measurements in circulating cell-free DNA to predict lack of benefit from pembrolizumab in patients with metastatic urothelial cancer.","authors":"Youssra Salhi, Stavros Makrodimitris, Sandra van Wilpe, Iris Te Paske, Vanja de Weerd, Corine M Beaufort, Hans M Westgeest, Jens Voortman, Maureen J B Aarts, Maud Rijnders, Astrid A M van der Veldt, Ronald de Wit, Niven Mehra, Saskia M Wilting, Debbie G J Robbrecht","doi":"10.1002/1878-0261.70272","DOIUrl":"10.1002/1878-0261.70272","url":null,"abstract":"Accurate prediction of lack of benefit from pembrolizumab in patients with metastatic urothelial cancer (mUC) is an unmet need. We investigated the dynamics of circulating tumor DNA (ctDNA) load, estimated using the modified fast aneuploidy screening test-sequencing system (mFast-SeqS), as a potential biomarker for early on-treatment identification of treatment response. A total of 104 patients with mUC treated with pembrolizumab from two prospective biomarker discovery trials were included and mFast-SeqS was performed on paired blood samples collected at baseline and on-treatment. Patients with a high on-treatment aneuploidy score (≥ 5, n = 26) had a shorter median OS than patients with a low (< 5) score (n = 76) (3 vs 17 months: P-value< 0.001). Patients with an increased (n = 10), stable (n = 66), or decreased (n = 28) on-treatment score relative to their baseline score had a median PFS of 1.5, 4.0, and 8.3 months, respectively. Median OS was 3.0, 11.1, and 18.7 months, respectively. In patients with mUC treated with pembrolizumab, the on-treatment mFast-SeqS-based ctDNA level and its dynamics relative to baseline are independent prognostic markers that can be used to identify patients that are unlikely to benefit from pembrolizumab.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"2175-2187"},"PeriodicalIF":4.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398679/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148258774","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}

引用次数: 0

RETRACTION: LncRNA AATBC Regulates Pinin to Promote Metastasis in Nasopharyngeal Carcinoma. 回撤：LncRNA AATBC调节Pinin促进鼻咽癌转移

IF 4.5 2区医学

Molecular Oncology Pub Date : 2026-09-01 Epub Date: 2026-08-07 DOI: 10.1002/1878-0261.70314

{"title":"RETRACTION: LncRNA AATBC Regulates Pinin to Promote Metastasis in Nasopharyngeal Carcinoma.","authors":"","doi":"10.1002/1878-0261.70314","DOIUrl":"10.1002/1878-0261.70314","url":null,"abstract":"Retraction: T. Tang, L. Yang, Y. Cao, M. Wang, S. Zhang, Z. Gong, F. Xiong, Y. He, Y. Zhou, Q. Liao, B. Xiang, M. Zhou, C. Guo, X. Li, Y. Li, W. Xiong, G. Li, and Z. Zeng, \"LncRNA AATBC Regulates Pinin to Promote Metastasis in Nasopharyngeal Carcinoma,\" Molecular Oncology 14, no. 9 (2020): 2251-2270, https://doi.org/10.1002/1878-0261.12703. The above article, published online on 4 May 2020 in Wiley Online Library (https://onlinelibrary.wiley.com/), has been retracted by agreement between the journal Editor-in-Chief, Kevin M. Ryan; the Federation of European Biochemical Societies; and John Wiley & Sons Ltd. The retraction has been agreed due to concerns raised by third parties. Specifically, image elements in Figures 2D and 2G were found to have been previously published by the author group in different scientific contexts. Furthermore, the GAPDH blots derived from the CNE2 cells for the \"NC\" and \"siPNN\" groups in Figure 4B, and for the \"NC\" and \"1237-3p\" groups in Figure 5C were found duplicated. In addition, overlapping regions were identified between the panels depicting the \"NC\" and \"siAATBC + PNN\" groups within the CNE2 lane. While the authors acknowledged the errors and supplied raw data in support of their response, the editors deemed the clarification insufficient to address their concerns. The authors attributed the mistakes to similarities between the affected images, raising concerns over the accuracy of the data presented in the remaining body of the article. Furthermore, further review determined that the vast majority of the cited references were self-citations, many of which were found to be irrelevant or only marginally relevant to the context at hand, resulting in several statements lacking adequate support from the literature. Accordingly, the article has been retracted, as the editors have lost confidence in the reliability of the results and conclusions presented. The authors have been informed of the retraction decision, but were not available for final confirmation.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"2384"},"PeriodicalIF":4.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13448557/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148684729","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}

引用次数: 0

ZW4864-mediated inhibition of the β-catenin/BCL9/BCL9L complex reveals therapeutic potential in bladder cancer. zw4864介导的β-catenin/BCL9/BCL9L复合物抑制揭示了膀胱癌的治疗潜力。

IF 4.5 2区医学

Molecular Oncology Pub Date : 2026-09-01 Epub Date: 2026-06-18 DOI: 10.1002/1878-0261.70292

Roland Kotolloshi, Mandy Berndt-Paetz, Eileen Lerner, Gregoire Najjar, Anca Azoitei, Krishna Pal Singh, Shailendra Kumar Gupta, Olaf Wolkenhauer, Cagatay Günes, Otmar Huber, Marc-Oliver Grimm, Daniel Steinbach

{"title":"ZW4864-mediated inhibition of the β-catenin/BCL9/BCL9L complex reveals therapeutic potential in bladder cancer.","authors":"Roland Kotolloshi, Mandy Berndt-Paetz, Eileen Lerner, Gregoire Najjar, Anca Azoitei, Krishna Pal Singh, Shailendra Kumar Gupta, Olaf Wolkenhauer, Cagatay Günes, Otmar Huber, Marc-Oliver Grimm, Daniel Steinbach","doi":"10.1002/1878-0261.70292","DOIUrl":"10.1002/1878-0261.70292","url":null,"abstract":"Bladder cancer is the most prevalent malignancy of the urinary tract; nevertheless, its progression and treatment continue to pose substantial challenges. While the molecular mechanisms underlying bladder cancer progression remain unknown, the Wnt/β-catenin signaling pathway has established roles in cancer progression. In this study, we investigated the contribution of BCL9(L) (coactivators of β-catenin) to bladder cancer progression and evaluated the therapeutic potential of disrupting the β-catenin/BCL9(L) complex. We demonstrate that BCL9L exerts oncogenic effects on the proliferation and invasion of bladder cancer cells and the knockdown of BCL9 also reduced the proliferation, migration, and invasion of bladder cancer cells, suggesting similar oncogenic roles. Pharmacological inhibition of the β-catenin/BCL9(L) complex using ZW4864 suppresses a subset of Wnt/β-catenin targets in bladder cancer cells, indicating the inhibition of canonical Wnt signaling. We show ZW4864 has an inhibitory effect on the proliferation, migration, and invasion of bladder cancer cells and impedes the growth and formation of multicellular bladder cancer organoids. These findings demonstrate the crucial role of BCL9 and BCL9L in bladder cancer progression and highlight the β-catenin/BCL9(L) axis as a promising therapeutic target.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"2296-2322"},"PeriodicalIF":4.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398921/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148278023","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}

引用次数: 0

Cancer cell-intrinsic type 1 interferon: production, signaling, and outcomes within sex-biased, female malignancies. 癌细胞内生性1型干扰素：在性别偏倚的女性恶性肿瘤中的产生、信号传导和结果

IF 4.5 2区医学

Molecular Oncology Pub Date : 2026-09-01 Epub Date: 2026-07-28 DOI: 10.1002/1878-0261.70311

Ashlyn Conant, Nora Badiner, Sharon Asariah, Kiera McGivney, Vishwa Shah, Tise Suzuki, Yevgeniya J Ioffe, Juli J Unternaehrer

{"title":"Cancer cell-intrinsic type 1 interferon: production, signaling, and outcomes within sex-biased, female malignancies.","authors":"Ashlyn Conant, Nora Badiner, Sharon Asariah, Kiera McGivney, Vishwa Shah, Tise Suzuki, Yevgeniya J Ioffe, Juli J Unternaehrer","doi":"10.1002/1878-0261.70311","DOIUrl":"10.1002/1878-0261.70311","url":null,"abstract":"Type 1 interferons (IFN-1), such as IFN-α and IFN-β, are the most well-studied interferon class due to their abundant expression, widespread signaling, and potent immunomodulatory functions. Although the role of these cytokines in mediating antiviral defense responses and immune activation has been well-studied, recent studies have suggested they play a more nuanced role in directing cell-autonomous responses in cancer. The role of cancer cell-autonomous IFN-1 production and signaling is complex and context dependent. IFN-1 has been shown to participate in both tumor-suppressing and -promoting activities based on the intensity and duration of the IFN-1 signal received. The cell-intrinsic roles appear to be immune-independent, mediating cancer cell responses to traditional therapies and regulating tumor progression. This review aimed to summarize the various roles of IFN-1 in cancer, with a focus on female-related malignancies-including ovarian, breast, cervical, and endometrial cancers-emphasizing the molecular mechanisms surrounding IFN-1 production and signaling, downstream functional outcomes, and therapeutic implications essential to understanding the pro- and antitumor roles of IFN-1.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"2135-2162"},"PeriodicalIF":4.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13415916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148605374","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}

引用次数: 0

Interferon beta drives therapy resistance in a patient-derived model of high-grade serous ovarian cancer. 干扰素在患者衍生的高级别浆液性卵巢癌模型中驱动治疗耐药性。

IF 4.5 2区医学

Molecular Oncology Pub Date : 2026-09-01 Epub Date: 2026-07-10 DOI: 10.1002/1878-0261.70305

Ashlyn Conant, Tise Suzuki, Kiera McGivney, V S S Abhinav Ayyadevara, Sharon Asariah, Jay Deng, Ethan Nyein, Jacqueline Coats, Gary Yu, Yevgeniya J Ioffe, Christian Hurtz, Juli J Unternaehrer

{"title":"Interferon beta drives therapy resistance in a patient-derived model of high-grade serous ovarian cancer.","authors":"Ashlyn Conant, Tise Suzuki, Kiera McGivney, V S S Abhinav Ayyadevara, Sharon Asariah, Jay Deng, Ethan Nyein, Jacqueline Coats, Gary Yu, Yevgeniya J Ioffe, Christian Hurtz, Juli J Unternaehrer","doi":"10.1002/1878-0261.70305","DOIUrl":"10.1002/1878-0261.70305","url":null,"abstract":"Type 1 interferon (IFN-1) production and signaling are frequently activated in response to DNA damage and have been associated with the development of therapy resistance in cancer. However, the cell-autonomous role of IFN-1 in driving resistance in high-grade serous ovarian cancer (HGSOC) remains unclear. Specifically, whether IFN-1 functions in HGSOC as solely a response to genotoxic stress due to genotoxic therapy as frontline treatment, or can independently act in driving resistance phenotypes, has not been studied. Utilizing a patient-derived model of cisplatin-sensitive (SE) and -resistant (CR) HGSOC, we demonstrate that chronic cisplatin exposure is associated with enrichment of IFN-1 signaling and an interferon-related DNA damage resistance signature. Acute cisplatin treatment elicited dynamic IFN-1 signaling in both SE and CR cells, indicating a conserved stress response. However, chronic, low-level exposure to exogenous IFNβ, without a DNA-damaging agent, phenocopied several features of chronic cisplatin-driven resistance, including reduced therapeutic sensitivity and decreased proliferation. Together, these findings identify IFNβ as a driver of resistance-associated phenotypes and highlight cell-autonomous IFN-1 signaling as a potential biomarker for resistance and therapeutic target in platinum-resistant disease.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"2323-2339"},"PeriodicalIF":4.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398636/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148422559","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}

引用次数: 0