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Cancers
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Recent Advances in Neuroblastoma Research
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Recent Advances in Neuroblastoma Research

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Pediatric Oncology".

Deadline for manuscript submissions: closed (30 April 2023) | Viewed by 25314

Special Issue Editors

Dr. John Inge Johnsen

E-Mail Website
Guest Editor
Childhood Cancer Research Unit, Department of Women’s and Children’s Health, Karolinska Institutet, 171 77 Stockholm, Sweden
Interests: neuroblastoma; pediatric cancer; tumor biology; translational research; preclinical tumor models
Prof. Dr. Per Kogner

E-Mail Website
Guest Editor
Childhood Cancer Research Unit, Department of Women’s and Children’s Health, Karolinska Institutet, 171 77 Stockholm, Sweden
Interests: neuroblastoma; pediatric cancer; tumor biology; translational research; preclinical tumor models

Special Issue Information

Dear Colleagues, 

Neuroblastoma research is dynamic and rapidly advancing at both the biological and clinical arena.

Neuroblastoma, a neural-crest-derived malignancy of the peripheral nervous system, is the most common and deadly tumor of infancy. Despite intensive multimodal therapies, survival for children with high-risk disease remains only slightly above 50%. The majority of patients with high-risk neuroblastoma have metastatic disease at diagnosis and even if initially cured, they are still at risk of relapse, where we currently have minimal chance for cure.

More detailed understanding of the causes, cellular origin, and plasticity of neuroblastoma as well as mechanisms of drug resistance, causes of metastatic spread, relapse, and progressive disease is required for developing and advancing more effective and less toxic therapeutic strategies for patient with neuroblastoma.

In this Special Issue of Cancers, we invite authors to contribute original research and review articles focusing on different aspects of neuroblastoma research, including development, mechanisms for metastatic spread and relapses, and strategies to study intra- and intercellular crosstalk of tumor cells and non-tumorigenic cells present in the tumor microenvironment. We will also consider articles on targeted therapeutic approaches, clinical advances, and epidemiological studies providing insights that may lead to better understanding and management as well as more effective therapies.

The collected articles in this Special Issue will further enhance our knowledge and understanding of neuroblastoma and drive the development of novel therapeutic strategies.

Dr. John Inge Johnsen
Prof. Dr. Per Kogner
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • neuroblastoma
  • developmental origin
  • cellular plasticity
  • preclinical models
  • targeted therapy
  • novel treatment

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Published Papers (7 papers)

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Editorial

Jump to: Research, Review

5 pages, 185 KiB  
Editorial
Recent Advances in Neuroblastoma Research
by John Inge Johnsen and Per Kogner
Cancers 2024, 16(4), 812; https://doi.org/10.3390/cancers16040812 - 17 Feb 2024
Cited by 4 | Viewed by 2697
Abstract
Neuroblastoma is a neural crest-derived tumor of the peripheral nervous system that is a leading cause of cancer-related deaths in children [...] Full article
(This article belongs to the Special Issue Recent Advances in Neuroblastoma Research)

Research

Jump to: Editorial, Review

13 pages, 4476 KiB  
Article
Dynamic Changes in Microvascular Density Can Predict Viable and Non-Viable Areas in High-Risk Neuroblastoma
by Laura Privitera, Layla Musleh, Irene Paraboschi, Olumide Ogunlade, Olumide Ogunbiyi, J. Ciaran Hutchinson, Neil Sebire, Paul Beard and Stefano Giuliani
Cancers 2023, 15(3), 917; https://doi.org/10.3390/cancers15030917 - 1 Feb 2023
Cited by 5 | Viewed by 2320
Abstract
Despite aggressive treatments, the prognosis of high-risk NB remains poor. Surgical oncology needs innovative intraoperative devices to help surgeons discriminate malignant tissue from necrotic and surrounding healthy tissues. Changes within the tumor vasculature could be used intraoperatively as a diagnostic tool to guide [...] Read more.
Despite aggressive treatments, the prognosis of high-risk NB remains poor. Surgical oncology needs innovative intraoperative devices to help surgeons discriminate malignant tissue from necrotic and surrounding healthy tissues. Changes within the tumor vasculature could be used intraoperatively as a diagnostic tool to guide surgical resection. Here, we retrospectively analyzed the mean vascular density (MVD) of different NB subtypes at diagnosis and after induction chemotherapy using scanned histological samples. One patient was prospectively enrolled, and an ex vivo photoacoustic imaging (PAI) scan was performed on two representative sections to assess its capacity to discriminate different tumor regions. We found that post-chemotherapy, viable areas of differentiating NBs and ganglioneuroblastomas are associated with higher MVD compared to poorly differentiated NBs. Early necrotic regions showed higher MVD than late necrotic and viable regions. Finally, calcified areas showed significantly lower MVD than any other histological component. The acquired PAI images showed a good high-resolution ex vivo 3D delineation of NB margins. Overall, these results suggest that a high-definition preclinical imaging device such as PAI could potentially be exploited to guide surgical resection by identifying different vasculature signatures. Full article
(This article belongs to the Special Issue Recent Advances in Neuroblastoma Research)
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21 pages, 4628 KiB  
Article
BET and CDK Inhibition Reveal Differences in the Proliferation Control of Sympathetic Ganglion Neuroblasts and Adrenal Chromaffin Cells
by Jessica Sriha, Caroline Louis-Brennetot, Cécile Pierre-Eugène, Sylvain Baulande, Virginie Raynal, Amira Kramdi, Igor Adameyko, Uwe Ernsberger, Thomas Deller, Olivier Delattre, Isabelle Janoueix-Lerosey and Hermann Rohrer
Cancers 2022, 14(11), 2755; https://doi.org/10.3390/cancers14112755 - 1 Jun 2022
Cited by 2 | Viewed by 2999
Abstract
Neuroblastoma arising from the adrenal differ from ganglionic neuroblastoma both genetically and clinically, with adrenal tumors being associated with a more severe prognosis. The different tumor properties may be linked to specific tumor founder cells in adrenal and sympathetic ganglia. To address this [...] Read more.
Neuroblastoma arising from the adrenal differ from ganglionic neuroblastoma both genetically and clinically, with adrenal tumors being associated with a more severe prognosis. The different tumor properties may be linked to specific tumor founder cells in adrenal and sympathetic ganglia. To address this question, we first set up cultures of mouse sympathetic neuroblasts and adrenal chromaffin cells. These cultures were then treated with various proliferation inhibitors to identify lineage-specific responses. We show that neuroblast and chromaffin cell proliferation was affected by WNT, ALK, IGF1, and PRC2/EZH2 signaling inhibitors to a similar extent. However, differential effects were observed in response to bromodomain and extraterminal (BET) protein inhibitors (JQ1, GSK1324726A) and to the CDK-7 inhibitor THZ1, with BET inhibitors preferentially affecting chromaffin cells, and THZ1 preferentially affecting neuroblasts. The differential dependence of chromaffin cells and neuroblasts on BET and CDK signaling may indicate different mechanisms during tumor initiation in sympathetic ganglia and adrenal. Full article
(This article belongs to the Special Issue Recent Advances in Neuroblastoma Research)
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24 pages, 6569 KiB  
Article
Cannabinol Inhibits Cellular Proliferation, Invasion, and Angiogenesis of Neuroblastoma via Novel miR-34a/tRiMetF31/PFKFB3 Axis
by Bo Wang, Dongping Li, Viktoriia Cherkasova, Marta Gerasymchuk, Aru Narendran, Igor Kovalchuk and Olga Kovalchuk
Cancers 2022, 14(8), 1908; https://doi.org/10.3390/cancers14081908 - 10 Apr 2022
Cited by 10 | Viewed by 3141
Abstract
High-risk neuroblastoma is an aggressive pediatric tumor. Despite great advances in neuroblastoma therapy and supportive care protocols, no curative treatment is available for most patients with this disease. Here, we uncover that CBN attenuated the cell proliferation, invasion, and angiogenesis of neuroblastoma cell [...] Read more.
High-risk neuroblastoma is an aggressive pediatric tumor. Despite great advances in neuroblastoma therapy and supportive care protocols, no curative treatment is available for most patients with this disease. Here, we uncover that CBN attenuated the cell proliferation, invasion, and angiogenesis of neuroblastoma cell lines in a dose-dependent manner via the inhibition of the AKT pathway and the upregulation of miR-34a that targets E2F1. Both miR-34a and a 31-nt tRNAiMet fragment (tRiMetF31) derived from miR-34a-guided cleavage were downregulated in 4 examined neuroblastoma cell lines inversely correlated with the levels of its direct target, the PFKFB3 protein. Moreover, ectopic tRiMetF31 suppressed proliferation, migration, and angiogenesis in the studied neuroblastoma cell lines. Conversely, tRiMetF31 knockdown promoted PFKFB3 expression, resulting in enhanced angiogenesis. Our findings reveal a suppressive role of CBN in neuroblastoma tumorigenesis, highlighting a novel and crucial miR-34a tumor suppressor network in CBN’s antineuroblastoma actions. Full article
(This article belongs to the Special Issue Recent Advances in Neuroblastoma Research)
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Review

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22 pages, 33085 KiB  
Review
Preclinical Models of Neuroblastoma—Current Status and Perspectives
by Ewa Krawczyk and Joanna Kitlińska
Cancers 2023, 15(13), 3314; https://doi.org/10.3390/cancers15133314 - 23 Jun 2023
Cited by 7 | Viewed by 3448
Abstract
Preclinical in vitro and in vivo models remain indispensable tools in cancer research. These classic models, including two- and three-dimensional cell culture techniques and animal models, are crucial for basic and translational studies. However, each model has its own limitations and typically does [...] Read more.
Preclinical in vitro and in vivo models remain indispensable tools in cancer research. These classic models, including two- and three-dimensional cell culture techniques and animal models, are crucial for basic and translational studies. However, each model has its own limitations and typically does not fully recapitulate the course of the human disease. Therefore, there is an urgent need for the development of novel, advanced systems that can allow for efficient evaluation of the mechanisms underlying cancer development and progression, more accurately reflect the disease pathophysiology and complexity, and effectively inform therapeutic decisions for patients. Preclinical models are especially important for rare cancers, such as neuroblastoma, where the availability of patient-derived specimens that could be used for potential therapy evaluation and screening is limited. Neuroblastoma modeling is further complicated by the disease heterogeneity. In this review, we present the current status of preclinical models for neuroblastoma research, discuss their development and characteristics emphasizing strengths and limitations, and describe the necessity of the development of novel, more advanced and clinically relevant approaches. Full article
(This article belongs to the Special Issue Recent Advances in Neuroblastoma Research)
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17 pages, 1466 KiB  
Review
Marine Cyanobacterial Peptides in Neuroblastoma: Search for Better Therapeutic Options
by Salman Ahmed, Waqas Alam, Michael Aschner, Rosanna Filosa, Wai San Cheang, Philippe Jeandet, Luciano Saso and Haroon Khan
Cancers 2023, 15(9), 2515; https://doi.org/10.3390/cancers15092515 - 27 Apr 2023
Cited by 8 | Viewed by 2822
Abstract
Neuroblastoma is the most prevalent extracranial solid tumor in pediatric patients, originating from sympathetic nervous system cells. Metastasis can be observed in approximately 70% of individuals after diagnosis, and the prognosis is poor. The current care methods used, which include surgical removal as [...] Read more.
Neuroblastoma is the most prevalent extracranial solid tumor in pediatric patients, originating from sympathetic nervous system cells. Metastasis can be observed in approximately 70% of individuals after diagnosis, and the prognosis is poor. The current care methods used, which include surgical removal as well as radio and chemotherapy, are largely unsuccessful, with high mortality and relapse rates. Therefore, attempts have been made to incorporate natural compounds as new alternative treatments. Marine cyanobacteria are a key source of physiologically active metabolites, which have recently received attention owing to their anticancer potential. This review addresses cyanobacterial peptides’ anticancer efficacy against neuroblastoma. Numerous prospective studies have been carried out with marine peptides for pharmaceutical development including in research for anticancer potential. Marine peptides possess several advantages over proteins or antibodies, including small size, simple manufacturing, cell membrane crossing capabilities, minimal drug–drug interactions, minimal changes in blood–brain barrier (BBB) integrity, selective targeting, chemical and biological diversities, and effects on liver and kidney functions. We discussed the significance of cyanobacterial peptides in generating cytotoxic effects and their potential to prevent cancer cell proliferation via apoptosis, the activation of caspases, cell cycle arrest, sodium channel blocking, autophagy, and anti-metastasis behavior. Full article
(This article belongs to the Special Issue Recent Advances in Neuroblastoma Research)
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29 pages, 1524 KiB  
Review
MYCN Impact on High-Risk Neuroblastoma: From Diagnosis and Prognosis to Targeted Treatment
by Damiano Bartolucci, Luca Montemurro, Salvatore Raieli, Silvia Lampis, Andrea Pession, Patrizia Hrelia and Roberto Tonelli
Cancers 2022, 14(18), 4421; https://doi.org/10.3390/cancers14184421 - 12 Sep 2022
Cited by 30 | Viewed by 6323
Abstract
Among childhood cancers, neuroblastoma is the most diffuse solid tumor and the deadliest in children. While to date, the pathology has become progressively manageable with a significant increase in 5-year survival for its less aggressive form, high-risk neuroblastoma (HR-NB) remains a major issue [...] Read more.
Among childhood cancers, neuroblastoma is the most diffuse solid tumor and the deadliest in children. While to date, the pathology has become progressively manageable with a significant increase in 5-year survival for its less aggressive form, high-risk neuroblastoma (HR-NB) remains a major issue with poor outcome and little survivability of patients. The staging system has also been improved to better fit patient needs and to administer therapies in a more focused manner in consideration of pathology features. New and improved therapies have been developed; nevertheless, low efficacy and high toxicity remain a staple feature of current high-risk neuroblastoma treatment. For this reason, more specific procedures are required, and new therapeutic targets are also needed for a precise medicine approach. In this scenario, MYCN is certainly one of the most interesting targets. Indeed, MYCN is one of the most relevant hallmarks of HR-NB, and many studies has been carried out in recent years to discover potent and specific inhibitors to block its activities and any related oncogenic function. N-Myc protein has been considered an undruggable target for a long time. Thus, many new indirect and direct approaches have been discovered and preclinically evaluated for the interaction with MYCN and its pathways; a few of the most promising approaches are nearing clinical application for the investigation in HR-NB. Full article
(This article belongs to the Special Issue Recent Advances in Neuroblastoma Research)
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