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Current Oncology
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New Therapeutic and Management Strategies for Childhood Cancers
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New Therapeutic and Management Strategies for Childhood Cancers

A special issue of Current Oncology (ISSN 1718-7729).

Deadline for manuscript submissions: closed (31 March 2023) | Viewed by 11145

Special Issue Editor

Dr. Saurabh Agarwal

E-Mail Website
Guest Editor
Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John’s University, New York, NY 11439, USA
Interests: pediatric cancers; neuroblastoma; cancer stem cells; metastasis; signaling pathways in cancer; immunotherapy; epigenetics; genetics; small molecule inhibitors; translational therapeutics; p53-myc interaction
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Childhood cancers are one of the leading causes of death among children. Treatment and management strategies for childhood cancers include chemotherapy, surgery, radiation, and stem cell transplantation. These therapeutic regimens are highly toxic and have long-lasting side effects, including secondary cancers in the future lifespan of pediatric patients. Despite these intensive therapeutic regimens, cancer may still relapse as a refractory and metastatic cancer. Therefore, understanding the causes of different childhood cancers, mechanisms of drug resistance, and causes of relapse and metastasis are required for developing and advancing the less-toxic and more-effective therapeutic and management strategies for childhood cancers. Recent advancements in developmental therapeutics and cancer management protocols are one step in this direction. In this Special Issue of Current Oncology, we invite authors to contribute original research and review articles focusing on different aspects of childhood or pediatric cancer development, causes, maintenance, and therapeutic strategies. We will also consider articles on developmental targeted therapeutic approaches pertaining to any childhood cancer including but not limited to acute lymphoblastic leukemia, acute myeloid leukemia, astrocytoma, oligodendroglioma, ependymoma, choroid plexus carcinoma, oligoastrocytoma, glioblastoma, ganglioglioma, desmoplastic infantile ganglioglioma, anaplastic ganglioglioma, gangliocytoma, medulloblastoma, rhabdomyosarcoma, pineocytoma, osteosarcoma, Ewing sarcoma, neuroblastoma, Wilms tumors, retinoblastoma, non-Hodgkin lymphoma,  Hodgkin lymphoma, hepatoblastoma, and hepatocellular carcinoma. The collected articles in this Special Issue will further enhance our knowledge and understanding of childhood cancers and drive the development of novel therapeutic and management strategies.

Dr. Saurabh Agarwal
Guest Editor

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2200 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

  • pediatric cancer
  • childhood cancer
  • cancer management
  • novel therapies
  • tumorigenesis
  • metastasis
  • relapse
  • small molecule inhibitors
  • therapeutics
  • chemotherapy

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Published Papers (4 papers)

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Research

11 pages, 2230 KiB  
Article
A Retrospective Study of Renal Growth Changes after Proton Beam Therapy for Pediatric Malignant Tumor
by Yinuo Li, Masashi Mizumoto, Yoshiko Oshiro, Hazuki Nitta, Takashi Saito, Takashi Iizumi, Chie Kawano, Yuni Yamaki, Hiroko Fukushima, Sho Hosaka, Kazushi Maruo, Satoshi Kamizawa and Hideyuki Sakurai
Curr. Oncol. 2023, 30(2), 1560-1570; https://doi.org/10.3390/curroncol30020120 - 24 Jan 2023
Cited by 4 | Viewed by 1695
Abstract
The purpose of this study was to analyze renal late effects after proton beam therapy (PBT) for pediatric malignant tumors. A retrospective study was performed in 11 patients under 8 years of age who received PBT between 2013 and 2018. The kidney was [...] Read more.
The purpose of this study was to analyze renal late effects after proton beam therapy (PBT) for pediatric malignant tumors. A retrospective study was performed in 11 patients under 8 years of age who received PBT between 2013 and 2018. The kidney was exposed in irradiation of the primary lesion in all cases. Kidney volume and contour were measured on CT or MRI. Dose volume was calculated with a treatment-planning system. The median follow-up was 24 months (range, 11–57 months). In irradiated kidneys and control contralateral kidneys, the median volume changes were −5.63 (−20.54 to 7.20) and 5.23 (−2.01 to 16.73) mL/year; and the median % volume changes at 1 year were −8.55% (−47.52 to 15.51%) and 9.53% (−2.13 to 38.78%), respectively. The median relative volume change for irradiated kidneys at 1 year was −16.42% (−52.21 to −4.53%) relative to control kidneys. Kidneys irradiated with doses of 10, 20, 30, 40, and 50 GyE had volume reductions of 0.16%, 0.90%, 1.24%, 2.34%, and 8.2% per irradiated volume, respectively. The larger the irradiated volume, the greater the kidney volume was lost. Volume reduction was much greater in patients aged 4–7 years than in those aged 2–3 years. The results suggest that kidneys exposed to PBT in treatment of pediatric malignant tumor show continuous atrophy in follow-up. The degree of atrophy is increased with a higher radiation dose, greater irradiated volume, and older age. However, with growth and maturation, the contralateral kidney becomes progressively larger and is less affected by radiation. Full article
(This article belongs to the Special Issue New Therapeutic and Management Strategies for Childhood Cancers)
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13 pages, 2017 KiB  
Article
Efficacy and Feasibility of Proton Beam Therapy in Relapsed High-Risk Neuroblastoma-Experiences from the Prospective KiProReg Registry
by Danny Jazmati, Barbara Hero, Theresa M. Thole.-Kliesch, Julien Merta, Hedwig E. Deubzer, Christian Bäumer, Feline Heinzelmann, Stefanie Schulze Schleithoff, Friederike Koerber, Angelika Eggert, Rudolf Schwarz, Thorsten Simon and Beate Timmermann
Curr. Oncol. 2022, 29(11), 8222-8234; https://doi.org/10.3390/curroncol29110649 - 30 Oct 2022
Cited by 3 | Viewed by 2669
Abstract
Background: Despite an intensive multimodal treatment approach, approximately 50% of high-risk (HR) neuroblastoma (NB) patients experience progression. Despite the advances in targeted therapy, high-dose chemotherapy, and other systemic treatment options, radiation therapy (RT) to sites of relapsed disease can be an option to [...] Read more.
Background: Despite an intensive multimodal treatment approach, approximately 50% of high-risk (HR) neuroblastoma (NB) patients experience progression. Despite the advances in targeted therapy, high-dose chemotherapy, and other systemic treatment options, radiation therapy (RT) to sites of relapsed disease can be an option to reduce tumor burden and improve chance for disease control. Methods: Patients who received salvage irradiation with proton beam therapy (PBT) for local or metastatic relapse of HR NB within the prospective registry trials KiProReg and ProReg were eligible for this retrospective analysis. Data on patient characteristics, multimodality therapy, adverse events, and oncologic endpoints were evaluated. Adverse events were assessed before, during, and after PBT according to common terminology criteria for adverse events (CTCAE) V4.0. Results: Between September 2013 and September 2020, twenty (11 male; 9 female) consecutive patients experiencing local (N = 9) or distant recurrence (N = 25) were identified for this analysis. Distant recurrences included osteomedullary (N = 11) or CNS lesions (N = 14). Salvage therapy consisted of re-induction chemo- or chemo-immuno-therapy (N = 19), surgery (N = 6), high-dose chemotherapy and stem cell transplantation (N = 13), radiation (N = 20), and concurrent systemic therapy. Systemic therapy concurrent to RT was given to six patients and included temozolomide (N = 4), carboplatine (N = 1), or anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK-TKI) (N = 1). A median dose of 36 Gy was applied to the 34 recurrent sites. Local RT was applied to 15 patients, while five patients, received craniospinal irradiation for CNS relapse. After a median follow-up (FU) of 20 months (4–66), the estimated rate for local control, distant metastatic free survival, and overall survival at 3 years was 68.0%, 37.9%, and 61.6%, respectively. During RT, ten patients (50%) presented with a higher-grade acute hematologic adverse event. Late higher-grade sequelae included transient myelitis with transverse section (N = 2) and secondary malignancy outside of the RT field (N = 1). Conclusion: Our study demonstrates the efficacy and safety of RT/PBT for recurrent HR NB in a multimodality second-line approach. To better define the role of RT for these patients, prospective studies would be desirable. Full article
(This article belongs to the Special Issue New Therapeutic and Management Strategies for Childhood Cancers)
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15 pages, 1641 KiB  
Article
Direct Targeting of the Raf-MEK-ERK Signaling Cascade Inhibits Neuroblastoma Growth
by Rameswari Chilamakuri and Saurabh Agarwal
Curr. Oncol. 2022, 29(9), 6508-6522; https://doi.org/10.3390/curroncol29090512 - 10 Sep 2022
Cited by 6 | Viewed by 2986
Abstract
The Raf-MEK-ERK signaling network has been the subject of intense research due to its role in the development of human cancers, including pediatric neuroblastoma (NB). MEK and ERK are the central components of this signaling pathway and are attractive targets for cancer therapy. [...] Read more.
The Raf-MEK-ERK signaling network has been the subject of intense research due to its role in the development of human cancers, including pediatric neuroblastoma (NB). MEK and ERK are the central components of this signaling pathway and are attractive targets for cancer therapy. Approximately 3–5% of the primary NB samples and about 80% of relapsed samples contain mutations in the Raf-MEK-ERK pathway. In the present study, we analyzed the NB patient datasets and revealed that high RAF and MEK expression leads to poor overall survival and directly correlates with cancer progression and relapse. Further, we repurposed a specific small-molecule MEK inhibitor CI-1040 to inhibit the Raf-MEK-ERK pathway in NB. Our results show that CI-1040 potently inhibits NB cell proliferation and clonogenic growth in a dose-dependent manner. Inhibition of the Raf-MEK-ERK pathway by CI-1040 significantly enhances apoptosis, blocks cell cycle progression at the S phase, inhibits expression of the cell cycle-related genes, and significantly inhibits phosphorylation and activation of the ERK1/2 protein. Furthermore, CI-1040 significantly inhibits tumor growth in different NB 3D spheroidal tumor models in a dose-dependent manner and by directly inhibiting spheroidal tumor cells. Overall, our findings highlight that direct inhibition of the Raf-MEK-ERK pathway is a novel therapeutic approach for NB, and further developing repurposing strategies using CI-1040 is a clinically tractable strategy for effectively treating NB. Full article
(This article belongs to the Special Issue New Therapeutic and Management Strategies for Childhood Cancers)
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15 pages, 313 KiB  
Article
The Use of Assisted Reproductive Technology by European Childhood Cancer Survivors
by Anja Borgmann-Staudt, Simon Michael, Greta Sommerhaeuser, Marta-Julia Fernández-González, Lucía Alacán Friedrich, Stephanie Klco-Brosius, Tomas Kepak, Jarmila Kruseova, Gisela Michel, Anna Panasiuk, Sandrin Schmidt, Laura Lotz and Magdalena Balcerek
Curr. Oncol. 2022, 29(8), 5748-5762; https://doi.org/10.3390/curroncol29080453 - 15 Aug 2022
Cited by 5 | Viewed by 2642
Abstract
CCS often wish to have biological children yet harbour concerns about fertility impairment, pregnancy risks and the general health risks of prospective offspring. To clarify these concerns, health outcomes in survivor offspring born following ART (n = 74, 4.5%) or after spontaneous [...] Read more.
CCS often wish to have biological children yet harbour concerns about fertility impairment, pregnancy risks and the general health risks of prospective offspring. To clarify these concerns, health outcomes in survivor offspring born following ART (n = 74, 4.5%) or after spontaneous conception (n = 1585) were assessed in our European offspring study by descriptive and bivariate analysis. Outcomes were compared to a sibling offspring cohort (n = 387) in a 4:1 matched-pair analysis (n = 1681). (i) Survivors were more likely to employ ART than their siblings (4.5% vs. 3.7%, p = 0.501). Successful pregnancies were achieved after a median of one cycle with, most commonly, intracytoplasmic sperm injection (ICSI) using non-cryopreserved oocytes/sperm. (ii) Multiple-sibling births (p < 0.001, 29.7% vs. 2.5%), low birth weight (p < 0.001; OR = 3.035, 95%-CI = 1.615–5.706), and preterm birth (p < 0.001; OR = 2.499, 95%-CI = 1.401–4.459) occurred significantly more often in survivor offspring following ART utilisation than in spontaneously conceived children. ART did not increase the prevalence of childhood cancer, congenital malformations or heart defects. (iii) These outcomes had similar prevalences in the sibling population. In our explorative study, we could not detect an influence on health outcomes when known confounders, such as multiple births, were taken into account. Full article
(This article belongs to the Special Issue New Therapeutic and Management Strategies for Childhood Cancers)
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