Molecular Oncology最新文献_第8页

Impact of molecular diagnostics and targeted cancer therapy on patient outcomes (MODIFY): a retrospective study of the implementation of precision oncology. 分子诊断和靶向癌症治疗对患者预后的影响（MODIFY）：精确肿瘤学实施的回顾性研究。

IF 6.6 2区医学

Molecular Oncology Pub Date : 2024-12-11 DOI: 10.1002/1878-0261.13785

Michaël Dang, Anna Schritz, Nikolai Goncharenko, Guy Berchem

{"title":"Impact of molecular diagnostics and targeted cancer therapy on patient outcomes (MODIFY): a retrospective study of the implementation of precision oncology.","authors":"Michaël Dang, Anna Schritz, Nikolai Goncharenko, Guy Berchem","doi":"10.1002/1878-0261.13785","DOIUrl":"https://doi.org/10.1002/1878-0261.13785","url":null,"abstract":"High-throughput genomic analyses are being implemented in clinical practice. MODIFY is a retrospective study of the first introduction of genomic profiling and molecular tumor boards in the country of Luxembourg. The primary objective was to assess whether patients derived a clinical benefit by measuring the percentage of patients who presented a progression-free survival (PFS) on matched therapy (PFS2) 1.3-fold longer than PFS on previous therapy (PFS1). A total of 94 patients were included. In total, 45 patients (53.57% of patients with successful next-generation sequencing [NGS] analysis) were found to have an actionable mutation. Of these, 11 patients received the treatment recommended by the molecular tumor board, another 12 received best-supportive care, and 20 were treated with conventional therapy. PFS2 and PFS1 data were available for eight patients. The PFS2/PFS1 ratio was ≥ -1.3 in 62.5% (n = 5/8; CI [30.38, 86.51]) of patients; three patients showed a partial response, and median overall survival (OS) was 7.3 months. Although the examined population was small, this study further supports evidence indicating that patients with advanced cancer benefit from molecular profiling and targeted therapy.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813700","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

SKA1 promotes oncogenic properties in oral dysplasia and oral squamous cell carcinoma, and augments resistance to radiotherapy. SKA1 促进口腔发育不良和口腔鳞状细胞癌的致癌特性，并增强对放射治疗的抵抗力。

IF 6.6 2区医学

Molecular Oncology Pub Date : 2024-12-10 DOI: 10.1002/1878-0261.13780

Alexander Michael Grandits, Barbara Andrea Reinoehl, Renate Wagner, Peter Kuess, Franziska Eckert, Anna Sophie Berghoff, Thorsten Fuereder, Rotraud Wieser

{"title":"SKA1 promotes oncogenic properties in oral dysplasia and oral squamous cell carcinoma, and augments resistance to radiotherapy.","authors":"Alexander Michael Grandits, Barbara Andrea Reinoehl, Renate Wagner, Peter Kuess, Franziska Eckert, Anna Sophie Berghoff, Thorsten Fuereder, Rotraud Wieser","doi":"10.1002/1878-0261.13780","DOIUrl":"https://doi.org/10.1002/1878-0261.13780","url":null,"abstract":"Oral squamous cell carcinoma (OSCC) is a malignancy associated with high morbidity and mortality, yet treatment options are limited. In addition to genetic alterations, aberrant gene expression contributes to the pathology of malignant diseases. In the present study, we identified 629 genes consistently dysregulated between OSCC and normal oral mucosa across nine public gene expression datasets. Among them, mitosis-related genes were significantly enriched, including spindle and kinetochore-associated complex subunit 1 (SKA1), whose roles in OSCC had been studied only to a very limited extent. We show that SKA1 promoted proliferation and colony formation in 2D and 3D, shortened the duration of metaphase, and increased the migration of OSCC cell lines. In addition, high SKA1 expression enhanced radioresistance, a previously unknown effect of this gene, which was accompanied by a reduction of radiation-induced senescence. SKA1 was also upregulated in a subset of advanced oral premalignancies and promoted tumor-relevant properties in a corresponding cell line. Gene expression patterns evoked by SKA1 overexpression confirmed that this gene is able to advance properties required for both early and advanced stages of tumorigenesis. In summary, our data show that SKA1 contributes to malignant progression in OSCC and may be a useful marker of radioresistance in this disease.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829427","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

Plasma-activated media selectively induces apoptotic death via an orchestrated oxidative stress pathway in high-grade serous ovarian cancer cells. 血浆激活介质通过精心安排的氧化应激途径选择性诱导高级别浆液性卵巢癌细胞的凋亡死亡。

IF 6.6 2区医学

Molecular Oncology Pub Date : 2024-12-03 DOI: 10.1002/1878-0261.13768

Lorena T Davies, Raja Ganesen, John Toubia, Sung-Ha Hong, Sushil Kumar Kc, Martin K Oehler, Carmela Ricciardelli, Endre J Szili, Nirmal Robinson, Melissa R Pitman

{"title":"Plasma-activated media selectively induces apoptotic death via an orchestrated oxidative stress pathway in high-grade serous ovarian cancer cells.","authors":"Lorena T Davies, Raja Ganesen, John Toubia, Sung-Ha Hong, Sushil Kumar Kc, Martin K Oehler, Carmela Ricciardelli, Endre J Szili, Nirmal Robinson, Melissa R Pitman","doi":"10.1002/1878-0261.13768","DOIUrl":"https://doi.org/10.1002/1878-0261.13768","url":null,"abstract":"High-grade serous ovarian cancer (HGSOC) is the most common and aggressive type of ovarian cancer. Due to a lack of an early detection test and overt symptoms, many patients are diagnosed at a late stage where metastasis makes treatment very challenging. Furthermore, the current standard treatment for HGSOC patients, consisting of debulking surgery and platinum-taxane chemotherapy, reduces quality of life due to debilitating side-effects. Sadly, 80-90% of patients diagnosed with advanced stage ovarian cancer will die due to treatment resistance. As such, novel therapeutic strategies for HGSOC that are both more effective and less toxic are urgently required. Here we describe the assessment of cold atmospheric pressure (CAP) gas discharge technology as a novel treatment strategy in pre-clinical models of HGSOC. Plasma-activated media (PAM) was generated using cell growth media. HGSOC cell lines, patient ascites cells and primary tissue explants were tested for their response to PAM via analysis of cell viability, cell death and oxidative stress assays. Our data show that PAM treatment can be more effective than standard carboplatin chemotherapy at selectively targeting ovarian cancer cells in primary patient samples. Further, we also observed PAM to induce apoptosis in HGSOC cancer cell lines via induction of oxidative stress and mitochondrial-mediated apoptosis. These findings suggest that PAM is a viable therapeutic strategy to test in in vivo models of ovarian cancer, with a view to develop an intraperitoneal PAM-based therapy for HGSOC patients. Our studies validate the ability of PAM to selectively target tumour tissue and ascites cells. This work supports the development of PAM towards in vivo validation and translation into clinical practice.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770547","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 CDK12-BRCA1 signaling axis mediates dinaciclib-associated radiosensitivity through p53-mediated cellular senescence. CDK12-BRCA1信号轴通过p53介导的细胞衰老介导与dicaciclib相关的放射敏感性。

IF 6.6 2区医学

Molecular Oncology Pub Date : 2024-12-03 DOI: 10.1002/1878-0261.13773

Natalia García Flores, Diego M Fernández-Aroca, Cristina Garnés-García, Andrés Domínguez-Calvo, Jaime Jiménez-Suárez, Sebastià Sabater, Pablo Fernández-Aroca, Ignacio Andrés, Francisco J Cimas, Guillermo de Cárcer, Borja Belandia, Ignacio Palmero, Pablo Huertas, María José Ruiz-Hidalgo, Ricardo Sánchez-Prieto

{"title":"The CDK12-BRCA1 signaling axis mediates dinaciclib-associated radiosensitivity through p53-mediated cellular senescence.","authors":"Natalia García Flores, Diego M Fernández-Aroca, Cristina Garnés-García, Andrés Domínguez-Calvo, Jaime Jiménez-Suárez, Sebastià Sabater, Pablo Fernández-Aroca, Ignacio Andrés, Francisco J Cimas, Guillermo de Cárcer, Borja Belandia, Ignacio Palmero, Pablo Huertas, María José Ruiz-Hidalgo, Ricardo Sánchez-Prieto","doi":"10.1002/1878-0261.13773","DOIUrl":"https://doi.org/10.1002/1878-0261.13773","url":null,"abstract":"Pan-cyclin-dependent-kinase (CDK) inhibitors are a new class of targeted therapies that can act on multiple CDKs, with dinaciclib being one of the most promising compounds. Although used as a monotherapy, an interesting approach could be to combine it with radiotherapy. Here, we show that dinaciclib increases radiosensitivity in some experimental models of lung and colon cancer (A549 or HCT 116) but not in others (H1299 or HT-29). Dinaciclib did not alter serine-protein kinase ATM signalling or cell cycle profiling after ionising-radiation exposure, which have been described for other CDK inhibitors. Interestingly, in terms of apoptosis, although the combination renders a clear increase, no potentiation of the ionising-radiation-induced apoptosis was observed. Mechanistically, inhibition of CDK12 by dinaciclib diminishes BRCA1 expression, which decreases homologous recombination (HR) and probably promotes the nonhomologous end joining repair process (NHEJ), which ultimately promotes the induction of ionising-radiation-associated cellular senescence in a TP53-dependent manner, explaining the lack of effect observed in some experimental models. In conclusion, our report proposes a molecular mechanism, based on the signalling axis CDK12-BRCA1, involved in this newly identified therapeutic effect of dinaciclib, although other players implicated in HR should not be discarded. In addition, our data provide a rationale for more selective and personalised chemo/radiotherapy treatment according to the genetic background of the tumour.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770616","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

Current status of precision oncology in adult glioblastoma. 成人胶质母细胞瘤精准肿瘤学的现状。

IF 6.6 2区医学

Molecular Oncology Pub Date : 2024-12-01 Epub Date: 2024-06-20 DOI: 10.1002/1878-0261.13678

Johannes Weller, Anna-Laura Potthoff, Thomas Zeyen, Christina Schaub, Cathrina Duffy, Matthias Schneider, Ulrich Herrlinger

{"title":"Current status of precision oncology in adult glioblastoma.","authors":"Johannes Weller, Anna-Laura Potthoff, Thomas Zeyen, Christina Schaub, Cathrina Duffy, Matthias Schneider, Ulrich Herrlinger","doi":"10.1002/1878-0261.13678","DOIUrl":"10.1002/1878-0261.13678","url":null,"abstract":"The concept of precision oncology, the application of targeted drugs based on comprehensive molecular profiling, has revolutionized treatment strategies in oncology. This review summarizes the current status of precision oncology in glioblastoma (GBM), the most common and aggressive primary brain tumor in adults with a median survival below 2 years. Targeted treatments without prior target verification have consistently failed. Patients with BRAF V600E-mutated GBM benefit from BRAF/MEK-inhibition, whereas targeting EGFR alterations was unsuccessful due to poor tumor penetration, tumor cell heterogeneity, and pathway redundancies. Systematic screening for actionable molecular alterations resulted in low rates (< 10%) of targeted treatments. Efficacy was observed in one-third and currently appears to be limited to BRAF-, VEGFR-, and mTOR-directed treatments. Advancing precision oncology for GBM requires consideration of pathways instead of single alterations, new trial concepts enabling rapid and adaptive drug evaluation, a focus on drugs with sufficient bioavailability in the CNS, and the extension of target discovery and validation to the tumor microenvironment, tumor cell networks, and their interaction with immune cells and neurons.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"2927-2950"},"PeriodicalIF":6.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11619805/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141427228","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

From bedside to bench: New insights in epilepsy-associated tumors based on recent classification updates and animal models on brain tumor networks. 从床边到工作台：基于最新分类更新和脑肿瘤网络动物模型的癫痫相关肿瘤新见解。

IF 6.6 2区医学

Molecular Oncology Pub Date : 2024-12-01 Epub Date: 2024-06-20 DOI: 10.1002/1878-0261.13680

Silvia Cases-Cunillera, Lea L Friker, Philipp Müller, Albert J Becker, Gerrit H Gielen

{"title":"From bedside to bench: New insights in epilepsy-associated tumors based on recent classification updates and animal models on brain tumor networks.","authors":"Silvia Cases-Cunillera, Lea L Friker, Philipp Müller, Albert J Becker, Gerrit H Gielen","doi":"10.1002/1878-0261.13680","DOIUrl":"10.1002/1878-0261.13680","url":null,"abstract":"Low-grade neuroepithelial tumors (LGNTs), particularly those with glioneuronal histology, are highly associated with pharmacoresistant epilepsy. Increasing research focused on these neoplastic lesions did not translate into drug discovery; and anticonvulsant or antitumor therapies are not available yet. During the last years, animal modeling has improved, thereby leading to the possibility of generating brain tumors in mice mimicking crucial genetic, molecular and immunohistological features. Among them, intraventricular in utero electroporation (IUE) has been proven to be a valuable tool for the generation of animal models for LGNTs allowing endogenous tumor growth within the mouse brain parenchyma. Epileptogenicity is mostly determined by the slow-growing patterns of these tumors, thus mirroring intrinsic interactions between tumor cells and surrounding neurons is crucial to investigate the mechanisms underlying convulsive activity. In this review, we provide an updated classification of the human LGNT and summarize the most recent data from human and animal models, with a focus on the crosstalk between brain tumors and neuronal function.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"2951-2965"},"PeriodicalIF":6.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11619802/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141427229","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

Unravelling the mosaic: Epigenetic diversity in glioblastoma. 揭开马赛克：胶质母细胞瘤的表观遗传多样性。

IF 6.6 2区医学

Molecular Oncology Pub Date : 2024-12-01 Epub Date: 2024-08-15 DOI: 10.1002/1878-0261.13706

Sara Lucchini, Myrianni Constantinou, Silvia Marino

引用次数: 0

Rodent models of tumours of the central nervous system. 中枢神经系统肿瘤的啮齿动物模型。

IF 6.6 2区医学

Molecular Oncology Pub Date : 2024-12-01 Epub Date: 2024-09-26 DOI: 10.1002/1878-0261.13729

Sebastian Brandner

{"title":"Rodent models of tumours of the central nervous system.","authors":"Sebastian Brandner","doi":"10.1002/1878-0261.13729","DOIUrl":"10.1002/1878-0261.13729","url":null,"abstract":"Modelling of human diseases is an essential component of biomedical research, to understand their pathogenesis and ultimately, develop therapeutic approaches. Here, we will describe models of tumours of the central nervous system, with focus on intrinsic CNS tumours. Model systems for brain tumours were established as early as the 1920s, using chemical carcinogenesis, and a systematic analysis of different carcinogens, with a more refined histological analysis followed in the 1950s and 1960s. Alternative approaches at the time used retroviral carcinogenesis, allowing a more topical, organ-centred delivery. Most of the neoplasms arising from this approach were high-grade gliomas. Whilst these experimental approaches did not directly demonstrate a cell of origin, the localisation and growth pattern of the tumours already pointed to an origin in the neurogenic zones of the brain. In the 1980s, expression of oncogenes in transgenic models allowed a more targeted approach by expressing the transgene under tissue-specific promoters, whilst the constitutive inactivation of tumour suppressor genes ('knock out')-often resulted in embryonic lethality. This limitation was elegantly solved by engineering the Cre-lox system, allowing for a promoter-specific, and often also time-controlled gene inactivation. More recently, the use of the CRISPR Cas9 technology has significantly increased experimental flexibility of gene expression or gene inactivation and thus added increased value of rodent models for the study of pathogenesis and establishing preclinical models.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"2842-2870"},"PeriodicalIF":6.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11619804/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350336","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

Microglia and macrophages in glioblastoma: landscapes and treatment directions. 胶质母细胞瘤中的小胶质细胞和巨噬细胞：景观和治疗方向。

IF 6.6 2区医学

Molecular Oncology Pub Date : 2024-12-01 Epub Date: 2024-05-07 DOI: 10.1002/1878-0261.13657

Georgios Solomou, Adam M H Young, Harry J C J Bulstrode

{"title":"Microglia and macrophages in glioblastoma: landscapes and treatment directions.","authors":"Georgios Solomou, Adam M H Young, Harry J C J Bulstrode","doi":"10.1002/1878-0261.13657","DOIUrl":"10.1002/1878-0261.13657","url":null,"abstract":"Glioblastoma is the most common primary malignant tumour of the central nervous system and remains uniformly and rapidly fatal. The tumour-associated macrophage (TAM) compartment comprises brain-resident microglia and bone marrow-derived macrophages (BMDMs) recruited from the periphery. Immune-suppressive and tumour-supportive TAM cell states predominate in glioblastoma, and immunotherapies, which have achieved striking success in other solid tumours have consistently failed to improve survival in this 'immune-cold' niche context. Hypoxic and necrotic regions in the tumour core are found to enrich, especially in anti-inflammatory and immune-suppressive TAM cell states. Microglia predominate at the invasive tumour margin and express pro-inflammatory and interferon TAM cell signatures. Depletion of TAMs, or repolarisation towards a pro-inflammatory state, are appealing therapeutic strategies and will depend on effective understanding and classification of TAM cell ontogeny and state based on new single-cell and spatial multi-omic in situ profiling. Here, we explore the application of these datasets to expand and refine TAM characterisation, to inform improved modelling approaches, and ultimately underpin the effective manipulation of function.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"2906-2926"},"PeriodicalIF":6.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11619806/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140851970","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

Understanding brain cancer and exploiting its vulnerabilities. 了解脑癌并利用其弱点。

IF 6.6 2区医学

Molecular Oncology Pub Date : 2024-12-01 Epub Date: 2024-11-25 DOI: 10.1002/1878-0261.13769

Paolo Salomoni

引用次数: 0