EJC paediatric oncology最新文献

{"title":"A review calling for research directed at early detection of childhood cancers: The clinical, scientific, and economic arguments for population screening and surveillance","authors":"John Apps ,&nbsp;Timothy A. Ritzmann ,&nbsp;JoFen Liu ,&nbsp;Dhurgshaarna Shanmugavadivel ,&nbsp;Christina Halsey ,&nbsp;Kathy Pritchard Jones ,&nbsp;Rifat Atun ,&nbsp;Kathy Oliver ,&nbsp;Kavita Vedhara ,&nbsp;Ashley Ball-Gamble ,&nbsp;Neil Ranasinghe ,&nbsp;Angela Polanco ,&nbsp;Jenny Adamski ,&nbsp;Adam L. Green ,&nbsp;David A. Walker","doi":"10.1016/j.ejcped.2024.100191","DOIUrl":"10.1016/j.ejcped.2024.100191","url":null,"abstract":"<div><div>Childhood cancers are increasingly recognised as disorders of tissue growth and development, through early life into adulthood. A rising proportion are currently considered to be related to a familial predisposition or associated with identified genetic mutations in predisposition genes. Their threat to life and risk of associated serious disability at diagnosis and need for complex life saving therapies makes them a research priority. Inadequate progress has been made in diagnosing childhood cancers earlier within global health systems, which means that their clinical presentations are either missed altogether or constitute high risk emergencies. Whilst knowledge of tumour biology has improved dramatically over the last decade due to the expansion in research technologies directed at innovative approaches to prognostication and treatment. A concerted research initiative to apply this knowledge to making the diagnosis of childhood cancers at earlier points in tumourgenesis has not developed. The risk for a child getting a cancer by the age of 5 is equivalent to the risks of the conditions selected as part of newborn population screening for rare inherited health conditions and is nearly 3 times that at age 18 years. We are proposing that research directed at accelerating cancer diagnosis for children by focussing upon feasibility and acceptability of linking targeted surveillance with population screening for all childhood cancers. This would be supported by enhanced public and professional awareness of a child’s risks of cancer and the range of clinical presentations. We suggest this must now be a top priority for research because of the potential for improving outcomes for treatment of all types of cancer and reducing the burden of disability and late effects of therapy.</div></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142437703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intermittent micafungin dosing schedule in pediatric oncology patients ‐ safe for outpatient parenteral antimicrobial therapy?","authors":"Jade A. Fox ,&nbsp;Nicolette Graham ,&nbsp;Rachael Lawson ,&nbsp;Sonya Stacey ,&nbsp;Julia E. Clark","doi":"10.1016/j.ejcped.2024.100189","DOIUrl":"10.1016/j.ejcped.2024.100189","url":null,"abstract":"<div><h3>Introduction</h3><div>Antifungal prophylaxis is an important preventative strategy for high-risk pediatric oncology patients. When triazoles are contraindicated, micafungin is an alternative to polyenes, due to improved tolerability and limited drug-drug interactions. An intermittent dosing schedule is advantageous for outpatient parenteral antimicrobial therapy (OPAT), but studies assessing safety in pediatric patients are limited.</div></div><div><h3>Methods</h3><div>This single-centre, retrospective, observational study compared the safety and tolerability of daily (1 mg/kg) and intermittent (3 mg/kg) dosing of amphotericin B liposomal (AmB) and micafungin in children under 18 years, with high-risk leukemia. Results</div><div>Of 51 patients, with 76 individual dosing schedules, hepatoxicity and nephrotoxicity were comparable across all four dosing schedules. Severity of hypokalemia was significantly higher amongst patients receiving AmB (p = 0.041), with higher rates of intravenous electrolyte supplementation required. Infusion-related reactions occurred only in the AmB group (22 %). Intermittent administration and dosing of micafungin was well tolerated, with similar effects on liver function and reduced rates of hypokalemia.</div></div><div><h3>Conclusion</h3><div>This study supports the positive safety profile of intermittent micafungin compared with AmB and describes successful OPAT implementation. Prospective studies assessing efficacy are needed to validate these findings.</div></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772610X24000497/pdfft?md5=fa11363a66340b24b7817e007bb8348e&pid=1-s2.0-S2772610X24000497-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142315218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Approved medicines for paediatric solid tumours in Europe: Lessons from the life cycle of a paediatric investigation plan","authors":"Erica Brivio ,&nbsp;Dominik Karres ,&nbsp;Giovanni Lesa ,&nbsp;Franca Ligas","doi":"10.1016/j.ejcped.2024.100190","DOIUrl":"10.1016/j.ejcped.2024.100190","url":null,"abstract":"<div><h3>Background</h3><p>Despite the positive changes brought by the Paediatric Regulation in the European Union (EU) in 2007, drug development in children remains challenging.</p></div><div><h3>Methods</h3><p>To better understand the issues encountered to reach an authorisation for paediatric patients, we reviewed the pathway of the 11 Paediatric Investigational Plans (PIPs) with indications targeting paediatric solid tumours granted by the Committee for Medicinal Products for Human Use (CHMP) between 2007 and 2022.</p></div><div><h3>Results</h3><p>On average 5,5 years were necessary to reach approval after a PIP was agreed. All the PIPs underwent at least one modification (median 3 modifications per PIP). The use of single arm trials, in the context of refractory/relapsed disease in absence of standard of care treatment, was supportive for granting a paediatric indication in the majority of the cases. In 6 out of 11 approved products, extrapolation from adults was used. For 2/11 the approval focused on an older population first compared to the initial age group agreed in the PIP due to the development of a suitable formulation for younger children still ongoing at the time of first approval. Scientific advice sought on paediatric development use of extrapolation from adults, major objections raised by CHMP and post-marketing requirements were examined.</p></div><div><h3>Conclusion</h3><p>Analysing the process necessary to reach an authorisation for paediatric patients, we highlight the major challenges faced in the paediatric approval process and the positive examples of successful drug development that reached final approval. Our analysis is expected to provide useful insights to drug developers, investigators and regulators.</p></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772610X24000503/pdfft?md5=0a6abf9fea2a487ca1cd504fccb08040&pid=1-s2.0-S2772610X24000503-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142240032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Common core variables for childhood cancer data integration","authors":"Daniela Di Carlo ,&nbsp;Ruth Ladenstein ,&nbsp;Norbert Graf ,&nbsp;Johannes Hans Merks ,&nbsp;Gustavo Hernández-Peñaloza ,&nbsp;Pamela Kearns ,&nbsp;Gianni Bisogno","doi":"10.1016/j.ejcped.2024.100186","DOIUrl":"10.1016/j.ejcped.2024.100186","url":null,"abstract":"<div><h3>Introduction</h3><p>Data-driven research has improved paediatric cancer outcomes for children. However, challenges in sharing data between institutions prevent the use of artificial intelligence (AI) to address substantial unmet needs in children diagnosed with cancer. Harmonising collected data can enable the application of AI for a greater understanding of paediatric cancers. The main goal of the paper was to analyse the currently used childhood cancer databases to identify a core of variables able to capture the most relevant data on the diagnosis and treatment of children and adolescents with cancer.</p></div><div><h3>Methods</h3><p>We arbitrarily identified different types of existing databases dedicated to collecting data of patients with solid tumours, Umbrella, FAR-RMS; PARTNER; ERN PAEDCAN Registry; INSTRUCT and INRG; the common data elements for Rare Disease by Joint Research Centre. The different elements of the CRFs were analysed and ranked “essential” and “good to have”. Domains that included a group of variables structurally connected were identified. Each variable was defined by name, data type, description, and permissible values.</p></div><div><h3>Results</h3><p>We identified six structural domains: Patient registration, Personal information, Disease History, Diagnosis, Treatment, and Follow-up and Events. For each of them, “essential” and “good to have” variables were defined.</p></div><div><h3>Discussion</h3><p>Data harmonisation is essential for enhancing integration and comparability in research. By standardizing data formats and variables, researchers can facilitate data sharing, collaboration, and analysis across multiple studies and datasets. Embracing data harmonization practices will advance application of AI, scientific knowledge, improve research reproducibility, and contribute to evidence-based decision-making in various fields.</p></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772610X24000461/pdfft?md5=fe6d34dd8fea9f6dd2eb50fc1c17e460&pid=1-s2.0-S2772610X24000461-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142094931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cross-border access to early phase clinical trials for children with cancer in the Nordic region","authors":"Sierra Alef-Defoe ,&nbsp;Solenne Carof ,&nbsp;Nanna Maria Hammer ,&nbsp;Sylvain Besle ,&nbsp;Hanne Baekgaard Larsen ,&nbsp;Britt Pinkowski Tersbøl ,&nbsp;Karsten Nysom","doi":"10.1016/j.ejcped.2024.100188","DOIUrl":"10.1016/j.ejcped.2024.100188","url":null,"abstract":"<div><h3>Introduction</h3><p>As 15 % of childhood cancers are still incurable, early phase clinical trials are essential in developing better therapies for children with cancer. Accessing relevant trials can be challenging, exacerbated by increasingly specialized therapies which are not available in every country. Copenhagen houses the main early phase trial center for children with cancer in the Nordic region, with about half of trial participants coming from abroad. We explored factors facilitating cross-border access to early phase pediatric cancer trials in Copenhagen.</p></div><div><h3>Methods and materials</h3><p>Interviews were conducted with 11 family members from five families and nineteen healthcare providers on socio-cultural aspects of traveling for the trial. A thematic analysis was conducted.</p></div><div><h3>Results</h3><p>Three major themes were identified: proximity to a trial center, facilitation of referral and logistics, and families’ and providers’ perceptions. Both geographic proximity and socio-cultural proximity facilitated access. Provider networks facilitated referrals and sponsors paid for travel, improving feasibility for families. Finally, families’ feelings of hope and providers’ positive perceptions of experimental therapy also promoted access to early phase trials.</p></div><div><h3>Conclusions</h3><p>Our findings highlight the importance of fully supporting families through logistics, expenses, and challenges associated with traveling to a clinical trial, the value of robust provider networks in facilitating referrals, and the need for awareness of potential socio-cultural bias in referring patients. While factors like geography and attitude also mitigate access, many barriers can be overcome by comprehensive support for families, improving access to early phase trials for children with cancer.</p></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772610X24000485/pdfft?md5=0db74d469eefaf7248a98a97b92e4013&pid=1-s2.0-S2772610X24000485-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142136387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical use-cases and implementation guidelines for the development of valuable AI","authors":"Karina C. Borja Jiménez ,&nbsp;Patrick Kemmeren ,&nbsp;Marry van den Heuvel-Ebrink ,&nbsp;Ronald de Krijger ,&nbsp;Martha Grootenhuis ,&nbsp;Marita Partanen ,&nbsp;Norbert Graf ,&nbsp;Shuping Wen ,&nbsp;Alexander Leemans ,&nbsp;Daniel L. Oberski ,&nbsp;Reineke A. Schoot ,&nbsp;Johannes H.M. Merks","doi":"10.1016/j.ejcped.2024.100187","DOIUrl":"10.1016/j.ejcped.2024.100187","url":null,"abstract":"<div><div>Contributing to UNICA4EU’s vision to upscale and wide-scale the application of AI technology to pediatric cancer care, this paper provides guidelines for the development of an AI-based ecosystem and its potential implementation into clinical practice. We also provide clinical use cases (UC) that depict scenarios at different stages of the patient journey and showcase how data collected through different methods and techniques interact and could synergize with AI tools to improve diagnosis and risk stratification, facilitate clinical decision making, and help to adequately monitor patients’ quality of life (QoL). Pediatric oncologists and AI specialists crafted each UC considering current standards, unmet needs, and advancements in both precision medicine and AI to address identified challenges. UC depict transferable methods and processes applicable to other diseases, and show how different techniques could ideally converge at different stages, representing a use case on its own.</div></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142534614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multimodality imaging of bone marrow involvement in paediatric oncology","authors":"Rutger A.J. Nievelstein ,&nbsp;Lise Borgwardt ,&nbsp;Thekla von Kalle ,&nbsp;Annemieke S. Littooij ,&nbsp;Lil-Sofie Ording Müller ,&nbsp;Nelleke Tolboom","doi":"10.1016/j.ejcped.2024.100185","DOIUrl":"10.1016/j.ejcped.2024.100185","url":null,"abstract":"<div><p>Identifying bone marrow involvement (with or without bone destruction) in children with cancer is essential for adequate diagnosis, prognostication, therapy planning, and response assessment. Imaging plays an increasing role, with MRI including DWI and [¹⁸F]FDG-PET/CT as the most commonly used imaging techniques. Interpretation of the paediatric bone marrow on imaging might be challenging because of age-related physiological changes in the bone marrow, as well as disease and therapy related effects. In this review, we discuss how the imaging techniques available may be employed to detect bone marrow involvement (BMI) in paediatric oncology. Furthermore, insights into physiological, disease and therapy related bone marrow changes in children that might influence bone marrow imaging interpretation will be provided.</p></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772610X2400045X/pdfft?md5=3aa84c07e24e27993735e5275b3f6424&pid=1-s2.0-S2772610X2400045X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142048735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cell state plasticity in neuroblastoma","authors":"Adam D. Durbin ,&nbsp;Rogier Versteeg","doi":"10.1016/j.ejcped.2024.100184","DOIUrl":"10.1016/j.ejcped.2024.100184","url":null,"abstract":"<div><p>Evolving evidence indicates that tumor cells can transdifferentiate between distinct transcriptionally-determined cell states with changes in resultant phenotypes, a phenomenon known as cellular plasticity. These transitions are not driven by genetic mutations and typically in contrast to normal developmental processes, may proceed bidirectionally. Here, we review the role of cellular plasticity in the aggressive childhood solid tumor, neuroblastoma. We discuss the detection of two cell states, termed mesenchymal (MES) and adrenergic (ADRN), their properties and the transcriptional circuitries that control them, their relation to the normal embryogenesis of the sympathetic nervous system and their potential role in drug resistance, escape from therapy and development of relapse.</p></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772610X24000448/pdfft?md5=c170b879fd46c55a60d589e9d6c2cdce&pid=1-s2.0-S2772610X24000448-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141997653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Re-irradiation for progressive Diffuse Intrinsic Pontine Glioma (DIPG): The Spanish experience","authors":"Elena Panizo-Morgado ,&nbsp;Felisa Vazquez-Gómez ,&nbsp;Marta Perez-Somarriba ,&nbsp;Miriam Pavon-Mengual ,&nbsp;Andrés Morales-La Madrid ,&nbsp;Blanca Lopez-Ibor ,&nbsp;Palma Solano ,&nbsp;Blanca Martinez de las Heras ,&nbsp;Marta Cortés-Hernández ,&nbsp;Miguel García-Ariza ,&nbsp;Roberto Carlos Raynero-Mellado ,&nbsp;Marta Martinez-Merino ,&nbsp;Ana de Lucio Delgado ,&nbsp;María Tallón-García ,&nbsp;Carmen Garrido-Colino ,&nbsp;Irene Ortiz-Gonzalez ,&nbsp;Raquel Portugal ,&nbsp;María Baro-Fernández ,&nbsp;Carmen Gonzalez San-Segundo ,&nbsp;Felipe Calvo ,&nbsp;Alvaro Lassaletta","doi":"10.1016/j.ejcped.2024.100183","DOIUrl":"10.1016/j.ejcped.2024.100183","url":null,"abstract":"<div><h3>Introduction</h3><p>Diffuse intrinsic pontine glioma (DIPG) is the most common malignant brainstem tumour in children. Despite advances in understanding its biology, current treatments have shown minimal impact on overall survival in this fatal disease. Focal radiotherapy (RT) is the only treatment proven to improve symptoms and extend progression-free survival. Albeit palliative, re-irradiation (rRT) has emerged as the best alternative for progressive disease. This study presents the Spanish experience with re-irradiation in DIPG.</p></div><div><h3>Results</h3><p>Between April 2015 and December 2023, 44 paediatric patients with progressive DIPG underwent rRT in 16 Spanish institutions. Median time from diagnosis to progression was 9.9 months (range, 4.2–24.3 months). Median dose of rRT was 20 Gy (range, 18–40 Gy) in 2 Gy fractions (range, 1.3–4 Gy). Twenty-two patients (50 %) received other treatments besides RT. Clinical improvement was seen in 77.3 %, and radiological improvement in 60 %. Treatment was well tolerated (1 case toxicity &gt;grade 2 related to rRT). Median overall survival was 15.5 months (range, 8.2–63.2 months), with a median time from rRT to death of 4.2 months (range, 0.6–10.3 months). Longer time between diagnosis and rRT (&gt;10 months) and dose of rRT &gt;20 Gy were statistically significantly correlated with better overall survival. There was no survival benefit in patients receiving additional treatments.</p></div><div><h3>Conclusions</h3><p>Re-irradiation is safe and effective in progressive DIPG patients, not only improving symptoms but also prolonging survival. However, the ideal candidates for rRT remain undefined, as well as the best irradiation scheme. Prospective studies are needed.</p></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772610X24000436/pdfft?md5=fcd1dc01981db6b28e802799b38274bd&pid=1-s2.0-S2772610X24000436-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141952191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MYCN in neuroblastoma: The kings' new clothes and drugs","authors":"Mareike Müller ,&nbsp;Katrin Trunk ,&nbsp;Daniel Fleischhauer ,&nbsp;Gabriele Büchel","doi":"10.1016/j.ejcped.2024.100182","DOIUrl":"10.1016/j.ejcped.2024.100182","url":null,"abstract":"<div><p>Deregulated levels of the MYCN oncogene contribute to the tumorigenesis of several human tumors including neuroblastoma. <em>MYCN</em> amplification classifies neuroendocrine tumors as high-risk and as a consequence is an unfavorable prognostic factor. MYCN has long been primarily described as a transcription factor, which binds to active promoters after heterodimerizing with MAX and directly regulates gene expression programs. New findings show that MYC proteins have novel oncogenic functions that are tumor-promoting and go beyond the regulation of gene expression. This review describes how MYCN continuously drives tumor progression by forming various protein complexes, for example to resolve torsional stress, coordinate transcription and replication, repair DNA damage and regulate R-loops. Interfering with the described processes as well as interfering with MYCN chromatin binding emerge as novel treatment strategies to indirectly target the oncoprotein. Furthermore, we describe the role of MYCN in metabolism and we review how these newly described functions of MYCN could be used as vulnerabilities for MYCN-driven tumors. Recent studies show that MYC proteins are capable of multimerizing at sites of genomic instability to protect cancer cells from stress. Additionally, MYCN can bind aberrant RNA transcripts, another feature to enhance the stress resilience of cancer cells, once again highlighting the oncogenic potential of MYC. Taken together, we show that the diverse functions of MYCN depend on its temporal and spatial dynamic interactome, making those interaction partners and functions crucial factors in the treatment of MYCN-related cancer.</p></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772610X24000424/pdfft?md5=a6328b571860cad1d591dd9876f1d23a&pid=1-s2.0-S2772610X24000424-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141847252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}