Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

Therapy Personalization in Pediatric Diseases: From Molecular Biology to Therapy

Special Issue Editors
Special Issue Information
Keywords
Published Papers

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 December 2020) | Viewed by 25756

Share This Special Issue

Special Issue Editors

Dr. Marianna Lucafò

E-Mail Website
Guest Editor

Institute for Maternal and Child Health -IRCCS "Burlo Garofolo", Trieste, Italy
Interests: inflammatory bowel disease; pediatrics; pharmacogenomics, translational medicine, intestinal organoids
Special Issues, Collections and Topics in MDPI journals

Dr. Giuliana Decorti

E-Mail Website
Guest Editor

1. Department of Medical, Surgical and Health Sciences, University of Trieste, Via Fleming, 22, 34127 Trieste, Italy
2. Institute for Maternal and Child Health - IRCCS "Burlo Garofolo", Via dell'Istria, 65, 34137 Trieste, Italy
Interests: pharmacogenetics; pharmacokinetics; pediatrics; inflammatory chronic diseases; acute lymphoblastic leukemia

Special Issue Information

Dear Colleagues,

Infants and children are not miniature adults, and the response to therapy in this population is different from that of adults. In addition, growth is not a linear process during the first decade of life; body composition and pharmacokinetic parameters are quickly changing, and drug response is therefore highly affected by developmental modifications. Therapy personalization during childhood therefore requires a thorough knowledge of developmental differences in pharmacokinetics. In addition, pharmacodynamic differences during development have also been described and recent research has focused on the ontogeny and developmental changes in transporters and receptor systems. Even pharmacogenetic determinants may play an important role in the response and toxicity of certain drugs and to age-dependent differences— particularly for chronic diseases. A better understanding of the molecular mechanisms and complexities that can explain the differences in drug handling and therapeutic responses between infants, children, and adults is mandatory for guiding pediatricians in their therapeutic decisions.

In this Special Issue, new evidence on the molecular landscape and pathophysiological mechanisms which are at the basis of the differences and peculiarities in drug therapy in the pediatric population will be addressed. This knowledge will result in a more rational approach to therapy in the pediatric patient, thus increasing its efficacy and safety.

Dr. Giuliana Decorti
Dr. Marianna Lucafò
Guest Editor

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 short 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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

pediatric patients
developmental changes
molecular mechanisms
personalized therapies
innovative therapies
pharmacogenomics
therapeutic drug monitoring
epigenetics
2D–3D disease modeling

Published Papers (7 papers)

Download All Papers

Research

Jump to: Review

30 pages, 4298 KiB

Open AccessArticle

Biological and Clinical Changes in a Pediatric Series Treated with Off-Label JAK Inhibitors

by Alessia Pin, Alessandra Tesser, Serena Pastore, Valentina Moressa, Erica Valencic, Anna Arbo, Alessandra Maestro, Alberto Tommasini and Andrea Taddio

Int. J. Mol. Sci. 2020, 21(20), 7767; https://doi.org/10.3390/ijms21207767 - 20 Oct 2020

Cited by 16 | Viewed by 2655

Abstract

Off-label use of medications is still a common practice in pediatric rheumatology. JAK inhibitors are authorized in adults in the treatment of rheumatoid arthritis, psoriatic arthritis and ulcerative colitis. Although their use is not authorized yet in children, JAK inhibitors, based on their mechanism of action and on clinical experiences in small series, have been suggested to be useful in the treatment of pediatric interferon-mediated inflammation. Accordingly, an increased interferon score may help to identify those patients who might benefit of JAK inhibitors. We describe the clinical experience with JAK inhibitors in seven children affected with severe inflammatory conditions and we discuss the correlation between clinical features and transcriptomic data. Clinical improvements were recorded in all cases. A reduction of interferon signaling was recorded in three out of seven subjects at last follow-up, irrespectively from clinical improvements. Other signal pathways with significant differences between patients and controls included upregulation of DNA repair pathway and downregulation of extracellular collagen homeostasis. Two patients developed drug-related adverse events, which were considered serious in one case. In conclusion, JAK inhibitors may offer a valuable option for children with severe interferon-mediated inflammatory disorders reducing the interferon score as well as influencing other signal pathways that deserve future studies. Full article

(This article belongs to the Special Issue Therapy Personalization in Pediatric Diseases: From Molecular Biology to Therapy)

► Show Figures

Figure 1

Review

Jump to: Research

22 pages, 398 KiB

Open AccessReview

Comprehensive Overview of Gene Rearrangements in Childhood T-Cell Acute Lymphoblastic Leukaemia

by Anna Mroczek, Joanna Zawitkowska, Jerzy Kowalczyk and Monika Lejman

Int. J. Mol. Sci. 2021, 22(2), 808; https://doi.org/10.3390/ijms22020808 - 15 Jan 2021

Cited by 8 | Viewed by 2924

Abstract

Acute lymphoblastic leukaemia (ALL) is a relevant form of childhood neoplasm, as it accounts for over 80% of all leukaemia cases. T-cell ALL constitutes a genetically heterogeneous cancer derived from T-lymphoid progenitors. The diagnosis of T-ALL is based on morphologic, immunophenotypic, cytogenetic, and molecular features, thus the results are used for patient stratification. Due to the expression of surface and intracellular antigens, several subtypes of T-ALL can be distinguished. Although the aetiology of T-ALL remains unclear, a wide spectrum of rearrangements and mutations affecting crucial signalling pathways has been described so far. Due to intensive chemotherapy regimens and supportive care, overall cure rates of more than 80% in paediatric T-ALL patients have been accomplished. However, improved knowledge of the mechanisms of relapse, drug resistance, and determination of risk factors are crucial for patients in the high-risk group. Even though some residual disease studies have allowed the optimization of therapy, the identification of novel diagnostic and prognostic markers is required to individualize therapy. The following review summarizes our current knowledge about genetic abnormalities in paediatric patients with T-ALL. As molecular biology techniques provide insights into the biology of cancer, our study focuses on new potential therapeutic targets and predictive factors which may improve the outcome of young patients with T-ALL. Full article

(This article belongs to the Special Issue Therapy Personalization in Pediatric Diseases: From Molecular Biology to Therapy)

21 pages, 2615 KiB

Open AccessReview

Neuroinflammation and Precision Medicine in Pediatric Neurocritical Care: Multi-Modal Monitoring of Immunometabolic Dysfunction

by Kristine E. Woodward, Pauline de Jesus and Michael J. Esser

Int. J. Mol. Sci. 2020, 21(23), 9155; https://doi.org/10.3390/ijms21239155 - 01 Dec 2020

Cited by 1 | Viewed by 2259

Abstract

The understanding of molecular biology in neurocritical care (NCC) is expanding rapidly and recognizing the important contribution of neuroinflammation, specifically changes in immunometabolism, towards pathological disease processes encountered across all illnesses in the NCC. Additionally, the importance of individualized inflammatory responses has been emphasized, acknowledging that not all individuals have the same mechanisms contributing towards their presentation. By understanding cellular processes that drive disease, we can make better personalized therapy decisions to improve patient outcomes. While the understanding of these cellular processes is evolving, the ability to measure such cellular responses at bedside to make acute care decisions is lacking. In this overview, we review cellular mechanisms involved in pathological neuroinflammation with a focus on immunometabolic dysfunction and review non-invasive bedside tools that have the potential to measure indirect and direct markers of shifts in cellular metabolism related to neuroinflammation. These tools include near-infrared spectroscopy, transcranial doppler, elastography, electroencephalography, magnetic resonance imaging and spectroscopy, and cytokine analysis. Additionally, we review the importance of genetic testing in providing information about unique metabolic profiles to guide individualized interpretation of bedside data. Together in tandem, these modalities have the potential to provide real time information and guide more informed treatment decisions. Full article

(This article belongs to the Special Issue Therapy Personalization in Pediatric Diseases: From Molecular Biology to Therapy)

► Show Figures

Figure 1

14 pages, 491 KiB

Open AccessReview

Insights on the Interplay between Cells Metabolism and Signaling: A Therapeutic Perspective in Pediatric Acute Leukemias

by Laura Anselmi, Salvatore Nicola Bertuccio, Annalisa Lonetti, Arcangelo Prete, Riccardo Masetti and Andrea Pession

Int. J. Mol. Sci. 2020, 21(17), 6251; https://doi.org/10.3390/ijms21176251 - 28 Aug 2020

Cited by 6 | Viewed by 2957

Abstract

Nowadays, thanks to extensive studies and progress in precision medicine, pediatric leukemia has reached an extremely high overall survival rate. Nonetheless, a fraction of relapses and refractory cases is still present, which are frequently correlated with poor prognosis. Although several molecular features of these diseases are known, still the field of energy metabolism, which is widely studied in adult, has not been frequently explored in childhood leukemias. Metabolic reprogramming is a hallmark of cancer and is deeply connected with other genetic and signaling aberrations generally known to be key features of both acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). This review aims to clear the current knowledge on metabolic rewiring in pediatric ALL and AML, also highlighting the influence of the main signaling pathways and suggesting potential ideas to further exploit this field to discover new prognostic biomarkers and, above all, beneficial therapeutic options. Full article

(This article belongs to the Special Issue Therapy Personalization in Pediatric Diseases: From Molecular Biology to Therapy)

► Show Figures

Figure 1

21 pages, 748 KiB

Open AccessReview

Phenotypes of Bronchopulmonary Dysplasia

by Shih-Hsin Wang and Po-Nien Tsao

Int. J. Mol. Sci. 2020, 21(17), 6112; https://doi.org/10.3390/ijms21176112 - 25 Aug 2020

Cited by 41 | Viewed by 5771

Abstract

Bronchopulmonary dysplasia (BPD) is the most common chronic morbidity in preterm infants. In the absence of effective interventions, BPD is currently a major therapeutic challenge. Several risk factors are known for this multifactorial disease that results in disrupted lung development. Inflammation plays an important role and leads to persistent airway and pulmonary vascular disease. Since corticosteroids are potent anti-inflammatory agents, postnatal corticosteroids have been used widely for BPD prevention and treatment. However, the clinical responses vary to a great degree across individuals, and steroid-related complications remain major concerns. Emerging studies on the molecular mechanism of lung alveolarization during inflammatory stress will elucidate the complicated pathway and help discover novel therapeutic targets. Moreover, with the advances in metabolomics, there are new opportunities to identify biomarkers for early diagnosis and prognosis prediction of BPD. Pharmacometabolomics is another novel field aiming to identify the metabolomic changes before and after a specific drug treatment. Through this “metabolic signature,” a more precise treatment may be developed, thereby avoiding unnecessary drug exposure in non-responders. In the future, more clinical, genetic, and translational studies would be required to improve the classification of BPD phenotypes and achieve individualized care to enhance the respiratory outcomes in preterm infants. Full article

(This article belongs to the Special Issue Therapy Personalization in Pediatric Diseases: From Molecular Biology to Therapy)

► Show Figures

Figure 1

25 pages, 774 KiB

Open AccessReview

Therapeutic Drug Monitoring Is a Feasible Tool to Personalize Drug Administration in Neonates Using New Techniques: An Overview on the Pharmacokinetics and Pharmacodynamics in Neonatal Age

by Domenico Umberto De Rose, Sara Cairoli, Marco Dionisi, Alessandra Santisi, Luca Massenzi, Bianca Maria Goffredo, Carlo Dionisi-Vici, Andrea Dotta and Cinzia Auriti

Int. J. Mol. Sci. 2020, 21(16), 5898; https://doi.org/10.3390/ijms21165898 - 17 Aug 2020

Cited by 30 | Viewed by 5498

Abstract

Therapeutic drug monitoring (TDM) should be adopted in all neonatal intensive care units (NICUs), where the most preterm and fragile babies are hospitalized and treated with many drugs, considering that organs and metabolic pathways undergo deep and progressive maturation processes after birth. Different developmental changes are involved in interindividual variability in response to drugs. A crucial point of TDM is the choice of the bioanalytical method and of the sample to use. TDM in neonates is primarily used for antibiotics, antifungals, and antiepileptic drugs in clinical practice. TDM appears to be particularly promising in specific populations: neonates who undergo therapeutic hypothermia or extracorporeal life support, preterm infants, infants who need a tailored dose of anticancer drugs. This review provides an overview of the latest advances in this field, showing options for a personalized therapy in newborns and infants. Full article

(This article belongs to the Special Issue Therapy Personalization in Pediatric Diseases: From Molecular Biology to Therapy)

► Show Figures

Figure 1

19 pages, 1207 KiB

Open AccessReview

Theragnostic Aspects and Radioimmunotherapy in Pediatric Tumors

by Andrea Cimini, Maria Ricci, Agostino Chiaravalloti, Luca Filippi and Orazio Schillaci

Int. J. Mol. Sci. 2020, 21(11), 3849; https://doi.org/10.3390/ijms21113849 - 28 May 2020

Cited by 30 | Viewed by 3253

Abstract

The use of theragnostic radiopharmaceuticals in nuclear medicine has grown rapidly over the years to combine the diagnosis and therapy of tumors. In this review, we performed web-based and desktop literature research to investigate and explain the potential role of theragnostic imaging in pediatric oncology. We focused primarily on patients with aggressive malignancies such as neuroblastoma and brain tumors, to select patients with the highest chance of benefit from personalized therapy. Moreover, the most critical and groundbreaking applications of radioimmunotherapy in children’s oncology were examined in this peculiar context. Preliminary results showed the potential feasibility of theragnostic imaging and radioimmunotherapy in pediatric oncology. They revealed advantages in the management of the disease, thereby allowing an intra-personal approach and adding new weapons to conventional therapies. Full article

(This article belongs to the Special Issue Therapy Personalization in Pediatric Diseases: From Molecular Biology to Therapy)

► Show Figures