Matej Jelic , Vasiliki Tzotzola , Daniela Di Carlo , Fabian Knörr , Miguel Vieira Martins , Fiona Poyer , Reineke A. Schoot , Emma Seaford , Maria Otth
{"title":"Young paediatric oncologists and haematologists in Europe – Emerging needs and future perspectives","authors":"Matej Jelic , Vasiliki Tzotzola , Daniela Di Carlo , Fabian Knörr , Miguel Vieira Martins , Fiona Poyer , Reineke A. Schoot , Emma Seaford , Maria Otth","doi":"10.1016/j.ejcped.2024.100192","DOIUrl":"10.1016/j.ejcped.2024.100192","url":null,"abstract":"<div><h3>Background</h3><div>The “Young NaPHOS” project was launched in 2021, by Young SIOPE, the group for junior members of the European Society for Paediatric Oncology (SIOPE). The Young NaPHOS project aims to build a network of national representatives of young paediatric haematologists and oncologists to discuss organisational and educational aspects at national and European level, differences in the training paths, and the needs to be addressed in the future.</div></div><div><h3>Methods</h3><div>From June 2021 until September 2022, three online meetings took place and one online survey was conducted. The meetings focused on presenting the structure and organisational aspects of existing national junior organisations in paediatric haematology and oncology, including their national activities. The survey aimed to investigate the European landscape of national organisations and training paths by inviting 39 young national representatives.</div></div><div><h3>Results</h3><div>Ten out of 34 responders confirmed the existence of a junior organisation in their country. Diversity was noted among the countries for the existence of such organisations, the organisations’ activities, or the membership criteria. Further, the training path to become a paediatric oncologist/haematologist differs a lot. Young paediatric oncologists also shared common concerns, especially regarding networking, international collaboration, and educational opportunities.</div></div><div><h3>Conclusion</h3><div>This project resulted in the creation of a European network among young paediatric oncologists and haematologists, in spreading ideas and offering support, and identified differences and areas for future action of Young SIOPE.</div></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":"4 ","pages":"Article 100192"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142417483","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}
Elizabeth Sokol , Brian LaBarre , Navin Pinto , Susan Kreissman , M. Meaghan Granger , Julie R. Park , Rochelle Bagatell , Arlene Naranjo , Steven G. DuBois
{"title":"Response to induction chemotherapy modifies the effect of conventional prognostic factors in high-risk neuroblastoma: A report from the Children’s Oncology Group","authors":"Elizabeth Sokol , Brian LaBarre , Navin Pinto , Susan Kreissman , M. Meaghan Granger , Julie R. Park , Rochelle Bagatell , Arlene Naranjo , Steven G. DuBois","doi":"10.1016/j.ejcped.2024.100193","DOIUrl":"10.1016/j.ejcped.2024.100193","url":null,"abstract":"<div><h3>Background</h3><div>Response to induction chemotherapy has been shown to predict outcome in patients with high-risk neuroblastoma (HR-NB), with those achieving a complete response (CR) having superior outcomes.</div></div><div><h3>Methods</h3><div>We evaluated whether conventional prognostic factors remain prognostic in subsets of patients defined by response to induction. 1244 Patients from four COG high-risk trials were included. End-induction response was coded as CR, partial response (PR) or better, less than PR without progressive disease (PD), and PD. Cox regression models were performed to calculate event-free and overall survival (EFS, OS) hazard ratios, including interaction terms between induction response and prognostic factors including sex, age, stage, primary tumor location, LDH, ferritin, ploidy, <em>MYCN</em> status, <em>ALK</em> status, histology, MKI, grade, and study era.</div></div><div><h3>Results</h3><div>Among patients who achieved a CR after induction, INSS stage 4 disease and trial era were the only factors that remained significantly associated with inferior OS. For those who achieved less than a PR, adrenal primary site, <em>MYCN</em> amplification, and 1p LOH were associated with inferior outcomes. Multivariable models showed that end-induction response remained prognostic of EFS and OS even after controlling for other factors. Multiple significant statistical interactions were observed between end-induction response and other prognostic factors.</div></div><div><h3>Conclusion</h3><div>The impact of conventional prognostic factors is not static in patients with HR-NB. Instead, response to induction chemotherapy modifies the effect of conventional prognostic factors. These data can help to further refine prognosis for patients with variable responses to induction and help to identify candidates who might benefit from treatment other than standard post-induction therapy.</div></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":"4 ","pages":"Article 100193"},"PeriodicalIF":0.0,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142417478","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}
John Apps , Timothy A. Ritzmann , JoFen Liu , Dhurgshaarna Shanmugavadivel , Christina Halsey , Kathy Pritchard Jones , Rifat Atun , Kathy Oliver , Kavita Vedhara , Ashley Ball-Gamble , Neil Ranasinghe , Angela Polanco , Jenny Adamski , Adam L. Green , David A. Walker
{"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 , Timothy A. Ritzmann , JoFen Liu , Dhurgshaarna Shanmugavadivel , Christina Halsey , Kathy Pritchard Jones , Rifat Atun , Kathy Oliver , Kavita Vedhara , Ashley Ball-Gamble , Neil Ranasinghe , Angela Polanco , Jenny Adamski , Adam L. Green , 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":"4 ","pages":"Article 100191"},"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}
Jade A. Fox , Nicolette Graham , Rachael Lawson , Sonya Stacey , Julia E. Clark
{"title":"Intermittent micafungin dosing schedule in pediatric oncology patients ‐ safe for outpatient parenteral antimicrobial therapy?","authors":"Jade A. Fox , Nicolette Graham , Rachael Lawson , Sonya Stacey , 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":"4 ","pages":"Article 100189"},"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}
Erica Brivio , Dominik Karres , Giovanni Lesa , Franca Ligas
{"title":"Approved medicines for paediatric solid tumours in Europe: Lessons from the life cycle of a paediatric investigation plan","authors":"Erica Brivio , Dominik Karres , Giovanni Lesa , 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":"4 ","pages":"Article 100190"},"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}
Daniela Di Carlo , Ruth Ladenstein , Norbert Graf , Johannes Hans Merks , Gustavo Hernández-Peñaloza , Pamela Kearns , Gianni Bisogno
{"title":"Common core variables for childhood cancer data integration","authors":"Daniela Di Carlo , Ruth Ladenstein , Norbert Graf , Johannes Hans Merks , Gustavo Hernández-Peñaloza , Pamela Kearns , 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":"4 ","pages":"Article 100186"},"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 , Solenne Carof , Nanna Maria Hammer , Sylvain Besle , Hanne Baekgaard Larsen , Britt Pinkowski Tersbøl , 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":"4 ","pages":"Article 100188"},"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}
Karina C. Borja Jiménez , Patrick Kemmeren , Marry van den Heuvel-Ebrink , Ronald de Krijger , Martha Grootenhuis , Marita Partanen , Norbert Graf , Shuping Wen , Alexander Leemans , Daniel L. Oberski , Reineke A. Schoot , Johannes H.M. Merks
{"title":"Clinical use-cases and implementation guidelines for the development of valuable AI","authors":"Karina C. Borja Jiménez , Patrick Kemmeren , Marry van den Heuvel-Ebrink , Ronald de Krijger , Martha Grootenhuis , Marita Partanen , Norbert Graf , Shuping Wen , Alexander Leemans , Daniel L. Oberski , Reineke A. Schoot , 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":"4 ","pages":"Article 100187"},"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}
Rutger A.J. Nievelstein , Lise Borgwardt , Thekla von Kalle , Annemieke S. Littooij , Lil-Sofie Ording Müller , Nelleke Tolboom
{"title":"Multimodality imaging of bone marrow involvement in paediatric oncology","authors":"Rutger A.J. Nievelstein , Lise Borgwardt , Thekla von Kalle , Annemieke S. Littooij , Lil-Sofie Ording Müller , 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 [<sup>18</sup>F]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":"4 ","pages":"Article 100185"},"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 , 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":"4 ","pages":"Article 100184"},"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}