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Cancers
Special Issues
Childhood Cancer in the Genomic Era: Experimental and Theoretical Approaches
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Childhood Cancer in the Genomic Era: Experimental and Theoretical Approaches

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (31 January 2023) | Viewed by 14259

Special Issue Editors

Dr. George I. Lambrou

E-Mail Website
Guest Editor
Choremeio Research Laboratory, First Department of Pediatrics, National and Kapodistrian University of Athens, Thivon & Levadeias 8, Goudi, 11527 Athens, Greece
Interests: tumor biology; physical biology; bioinformatics; cell biology
Dr. Maria Braoudaki

E-Mail Website
Guest Editor
Department of Clinical, Pharmaceutical and Biological Science, School of Life and Health Sciences, University of Hertfordshire, Hertfordshire AL10 9AB, UK
Interests: epigenetics; microarrays; proteomics; RNA-seq; next generation sequencing; transcriptomics; bioinformatics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

I invite you to contribute to the Special Issue of the journal Cancers entitled “Childhood Cancer in the Genomic Era: Experimental and Theoretical Approaches”, which aims to present recent developments in the field of childhood cancer from all perspectives, including both experimental and theoretical.

Cancer is one of the leading causes of death in the modern world. Childhood cancer in particular is a special case, first of all due to the sensitivity of this population but most importantly due to the devastating effects the disease has on children. Modern tools and methodologies allow the discovery and detection of a plethora of molecules toward the unraveling of tumor mechanics and therefore of childhood tumor mechanics. In that sense, the present Special Issue is dedicated to the description and study of childhood cancer from all its aspects. These include but are not limited to gene expression (including all available methods), protein expression, modeling, systems analysis and biology, bioinformatics approaches, epidemiology, mutation analyses, metabolomics, epigenetics, big data in tumor biology and research, theoretical aspects of modeling in childhood neoplasms, bioethics of childhood genomic research, etc.

Thus, I invite you to submit your research on this topic, in the form of original research papers, mini-reviews, and perspective articles.

Keywords

  • microarrays
  • NGS
  • mutation analysis
  • CNV
  • epigenetics
  • modeling
  • mathematical models
  • physical models

Published Papers (6 papers)

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Research

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15 pages, 1175 KiB  
Article
Deep Learning Approaches to Osteosarcoma Diagnosis and Classification: A Comparative Methodological Approach
by Ioannis A. Vezakis, George I. Lambrou and George K. Matsopoulos
Cancers 2023, 15(8), 2290; https://doi.org/10.3390/cancers15082290 - 13 Apr 2023
Cited by 4 | Viewed by 1709
Abstract
Background: Osteosarcoma is the most common primary malignancy of the bone, being most prevalent in childhood and adolescence. Despite recent progress in diagnostic methods, histopathology remains the gold standard for disease staging and therapy decisions. Machine learning and deep learning methods have shown [...] Read more.
Background: Osteosarcoma is the most common primary malignancy of the bone, being most prevalent in childhood and adolescence. Despite recent progress in diagnostic methods, histopathology remains the gold standard for disease staging and therapy decisions. Machine learning and deep learning methods have shown potential for evaluating and classifying histopathological cross-sections. Methods: This study used publicly available images of osteosarcoma cross-sections to analyze and compare the performance of state-of-the-art deep neural networks for histopathological evaluation of osteosarcomas. Results: The classification performance did not necessarily improve when using larger networks on our dataset. In fact, the smallest network combined with the smallest image input size achieved the best overall performance. When trained using 5-fold cross-validation, the MobileNetV2 network achieved 91% overall accuracy. Conclusions: The present study highlights the importance of careful selection of network and input image size. Our results indicate that a larger number of parameters is not always better, and the best results can be achieved on smaller and more efficient networks. The identification of an optimal network and training configuration could greatly improve the accuracy of osteosarcoma diagnoses and ultimately lead to better disease outcomes for patients. Full article
(This article belongs to the Special Issue Childhood Cancer in the Genomic Era: Experimental and Theoretical Approaches)
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20 pages, 576 KiB  
Article
Mathematical Model of Clonal Evolution Proposes a Personalised Multi-Modal Therapy for High-Risk Neuroblastoma
by Matteo Italia, Kenneth Y. Wertheim, Sabine Taschner-Mandl, Dawn Walker and Fabio Dercole
Cancers 2023, 15(7), 1986; https://doi.org/10.3390/cancers15071986 - 26 Mar 2023
Cited by 4 | Viewed by 2424
Abstract
Neuroblastoma is the most common extra-cranial solid tumour in children. Despite multi-modal therapy, over half of the high-risk patients will succumb. One contributing factor is the one-size-fits-all nature of multi-modal therapy. For example, during the first step (induction chemotherapy), the standard regimen (rapid [...] Read more.
Neuroblastoma is the most common extra-cranial solid tumour in children. Despite multi-modal therapy, over half of the high-risk patients will succumb. One contributing factor is the one-size-fits-all nature of multi-modal therapy. For example, during the first step (induction chemotherapy), the standard regimen (rapid COJEC) administers fixed doses of chemotherapeutic agents in eight two-week cycles. Perhaps because of differences in resistance, this standard regimen results in highly heterogeneous outcomes in different tumours. In this study, we formulated a mathematical model comprising ordinary differential equations. The equations describe the clonal evolution within a neuroblastoma tumour being treated with vincristine and cyclophosphamide, which are used in the rapid COJEC regimen, including genetically conferred and phenotypic drug resistance. The equations also describe the agents’ pharmacokinetics. We devised an optimisation algorithm to find the best chemotherapy schedules for tumours with different pre-treatment clonal compositions. The optimised chemotherapy schedules exploit the cytotoxic difference between the two drugs and intra-tumoural clonal competition to shrink the tumours as much as possible during induction chemotherapy and before surgical removal. They indicate that induction chemotherapy can be improved by finding and using personalised schedules. More broadly, we propose that the overall multi-modal therapy can be enhanced by employing targeted therapies against the mutations and oncogenic pathways enriched and activated by the chemotherapeutic agents. To translate the proposed personalised multi-modal therapy into clinical use, patient-specific model calibration and treatment optimisation are necessary. This entails a decision support system informed by emerging medical technologies such as multi-region sequencing and liquid biopsies. The results and tools presented in this paper could be the foundation of this decision support system. Full article
(This article belongs to the Special Issue Childhood Cancer in the Genomic Era: Experimental and Theoretical Approaches)
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20 pages, 7154 KiB  
Article
Deregulated Gene Expression Profiles and Regulatory Networks in Adult and Pediatric RUNX1/RUNX1T1-Positive AML Patients
by Peggy Kanellou, Ilias Georgakopoulos-Soares and Apostolos Zaravinos
Cancers 2023, 15(6), 1795; https://doi.org/10.3390/cancers15061795 - 16 Mar 2023
Viewed by 2118
Abstract
Acute myeloid leukemia (AML) is a heterogeneous and complex disease concerning molecular aberrations and prognosis. RUNX1/RUNX1T1 is a fusion oncogene that results from the chromosomal translocation t(8;21) and plays a crucial role in AML. However, its impact on the transcriptomic profile of different [...] Read more.
Acute myeloid leukemia (AML) is a heterogeneous and complex disease concerning molecular aberrations and prognosis. RUNX1/RUNX1T1 is a fusion oncogene that results from the chromosomal translocation t(8;21) and plays a crucial role in AML. However, its impact on the transcriptomic profile of different age groups of AML patients is not completely understood. Here, we investigated the deregulated gene expression (DEG) profiles in adult and pediatric RUNX1/RUNX1T1-positive AML patients, and compared their functions and regulatory networks. We retrospectively analyzed gene expression data from two independent Gene Expression Omnibus (GEO) datasets (GSE37642 and GSE75461) and computed their differentially expressed genes and upstream regulators, using limma, GEO2Enrichr, and X2K. For validation purposes, we used the TCGA-LAML (adult) and TARGET-AML (pediatric) patient cohorts. We also analyzed the protein–protein interaction (PPI) networks, as well as those composed of transcription factors (TF), intermediate proteins, and kinases foreseen to regulate the top deregulated genes in each group. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analyses were further performed for the DEGs in each dataset. We found that the top upregulated genes in (both adult and pediatric) RUNX1/RUNX1T1-positive AML patients are enriched in extracellular matrix organization, the cell projection membrane, filopodium membrane, and supramolecular fiber. Our data corroborate that RUNX1/RUNX1T1 reprograms a large transcriptional network to establish and maintain leukemia via intricate PPI interactions and kinase-driven phosphorylation events. Full article
(This article belongs to the Special Issue Childhood Cancer in the Genomic Era: Experimental and Theoretical Approaches)
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Review

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27 pages, 834 KiB  
Review
Genomics-Driven Precision Medicine in Pediatric Solid Tumors
by Praewa Suthapot, Wararat Chiangjong, Parunya Chaiyawat, Pongsakorn Choochuen, Dumnoensun Pruksakorn, Surasak Sangkhathat, Suradej Hongeng, Usanarat Anurathapan and Somchai Chutipongtanate
Cancers 2023, 15(5), 1418; https://doi.org/10.3390/cancers15051418 - 23 Feb 2023
Viewed by 2473
Abstract
Over the past decades, several study programs have conducted genetic testing in cancer patients to identify potential genetic targets for the development of precision therapeutic strategies. These biomarker-driven trials have demonstrated improved clinical outcomes and progression-free survival rates in various types of cancers, [...] Read more.
Over the past decades, several study programs have conducted genetic testing in cancer patients to identify potential genetic targets for the development of precision therapeutic strategies. These biomarker-driven trials have demonstrated improved clinical outcomes and progression-free survival rates in various types of cancers, especially for adult malignancies. However, similar progress in pediatric cancers has been slow due to their distinguished mutation profiles compared to adults and the low frequency of recurrent genomic alterations. Recently, increased efforts to develop precision medicine for childhood malignancies have led to the identification of genomic alterations and transcriptomic profiles of pediatric patients which presents promising opportunities to study rare and difficult-to-access neoplasms. This review summarizes the current state of known and potential genetic markers for pediatric solid tumors and provides perspectives on precise therapeutic strategies that warrant further investigations. Full article
(This article belongs to the Special Issue Childhood Cancer in the Genomic Era: Experimental and Theoretical Approaches)
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16 pages, 732 KiB  
Review
A Comprehensive Overview of Recent Advances in Epigenetics in Pediatric Acute Lymphoblastic Leukemia
by Paulina Drożak, Łukasz Bryliński and Joanna Zawitkowska
Cancers 2022, 14(21), 5384; https://doi.org/10.3390/cancers14215384 - 01 Nov 2022
Cited by 5 | Viewed by 2068
Abstract
Recent years have brought a novel insight into our understanding of childhood acute lymphoblastic leukemia (ALL), along with several breakthrough treatment methods. However, multiple aspects of mechanisms behind this disease remain to be elucidated. Evidence suggests that leukemogenesis in ALL is widely influenced [...] Read more.
Recent years have brought a novel insight into our understanding of childhood acute lymphoblastic leukemia (ALL), along with several breakthrough treatment methods. However, multiple aspects of mechanisms behind this disease remain to be elucidated. Evidence suggests that leukemogenesis in ALL is widely influenced by epigenetic modifications. These changes include: DNA hypermethylation, histone modification and miRNA alteration. DNA hypermethylation in promoter regions, which leads to silencing of tumor suppressor genes, is a common epigenetic alteration in ALL. Histone modifications are mainly caused by an increased expression of histone deacetylases. A dysregulation of miRNA results in changes in the expression of their target genes. To date, several hundred genes were identified as suppressed by epigenetic mechanisms in ALL. What is promising is that epigenetic alterations in ALL may be used as potential biomarkers for classification of subtypes, predicting relapse and disease progression and assessing minimal residual disease. Furthermore, since epigenetic lesions are potentially reversible, an activation of epigenetically silenced genes with the use of hypomethylating agents or histone deacetylase inhibitors may be utilized as a therapeutic strategy for ALL. The following review summarizes our current knowledge about epigenetic modifications in ALL and describes potential uses of epigenetics in the clinical management of this disease. Full article
(This article belongs to the Special Issue Childhood Cancer in the Genomic Era: Experimental and Theoretical Approaches)
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28 pages, 2253 KiB  
Review
Molecular Engines, Therapeutic Targets, and Challenges in Pediatric Brain Tumors: A Special Emphasis on Hydrogen Sulfide and RNA-Based Nano-Delivery
by Sherif Ashraf Fahmy, Alyaa Dawoud, Yousra Ahmed Zeinelabdeen, Caroline Joseph Kiriacos, Kerolos Ashraf Daniel, Omar Eltahtawy, Miriam Mokhtar Abdelhalim, Maria Braoudaki and Rana A. Youness
Cancers 2022, 14(21), 5244; https://doi.org/10.3390/cancers14215244 - 26 Oct 2022
Cited by 19 | Viewed by 2762
Abstract
Pediatric primary brain tumors represent a real challenge in the oncology arena. Besides the psychosocial burden, brain tumors are considered one of the most difficult-to-treat malignancies due to their sophisticated cellular and molecular pathophysiology. Notwithstanding the advances in research and the substantial efforts [...] Read more.
Pediatric primary brain tumors represent a real challenge in the oncology arena. Besides the psychosocial burden, brain tumors are considered one of the most difficult-to-treat malignancies due to their sophisticated cellular and molecular pathophysiology. Notwithstanding the advances in research and the substantial efforts to develop a suitable therapy, a full understanding of the molecular pathways involved in primary brain tumors is still demanded. On the other hand, the physiological nature of the blood–brain barrier (BBB) limits the efficiency of many available treatments, including molecular therapeutic approaches. Hydrogen Sulfide (H2S), as a member of the gasotransmitters family, and its synthesizing machinery have represented promising molecular targets for plentiful cancer types. However, its role in primary brain tumors, generally, and pediatric types, particularly, is barely investigated. In this review, the authors shed the light on the novel role of hydrogen sulfide (H2S) as a prominent player in pediatric brain tumor pathophysiology and its potential as a therapeutic avenue for brain tumors. In addition, the review also focuses on the challenges and opportunities of several molecular targeting approaches and proposes promising brain-delivery strategies for the sake of achieving better therapeutic results for brain tumor patients. Full article
(This article belongs to the Special Issue Childhood Cancer in the Genomic Era: Experimental and Theoretical Approaches)
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