Drug repurposing towards targeting cancer stem cells in pediatric brain tumors

AbstractIn the pediatric population, brain tumors represent the most commonly diagnosed solid neoplasms and the leading cause of cancer-related deaths globally. They include low-grade gliomas (LGGs), medulloblastomas (MBs), and other embryonal, ependymal, and neuroectodermal tumors. The mainstay of treatment for most brain tumors includes surgical intervention, radiation therapy, and chemotherapy. However, resistance to conventional therapy is widespread, which contributes to the high mortality rates reported and lack of improvement in patient survival despite advancement in therapeutic research. This has been attributed to the presence of a subpopulation of cells, known as cancer stem cells (CSCs), which reside within the tumor bulk and maintain self-renewal and recurrence potential of the tumor. An emerging promising approach that enables identifying novel therapeutic strategies to target CSCs and overcome therapy resistance is drug repurposing or repositioning. This is based on using previously approved drugs with known pharmacokinetic and pharmacodynamic characteristics for indications other than their traditional ones, like cancer. In this review, we provide a synopsis of the drug repurposing methodologies that have been used in pediatric brain tumors, and we argue how this selective compilation of approaches, with a focus on CSC targeting, could elevate drug repurposing to the next level.
Source: Cancer and Metastasis Reviews - Category: Cancer & Oncology Source Type: research

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AbstractBackgroundPrevious studies have identified that patients withEGFR mutations tend to have better responses to targeted therapy, as well as chemotherapy; however, the effect of genetic alterations in terms of radiotherapy (RT) ‐related outcomes has not been fully assessed. We studied the impact of common non‐small cell lung cancer (NSCLC) genetic alterations (EGFR,ALK andKRAS) in relation to objective response rate (ORR) to RT in patients with brain metastases.MethodsFrom 2009 –2015, 153 patients with an available genotyping status were treated with whole‐brain irradiation (WBI) before receiving systemic ...
Source: Thoracic Cancer - Category: Cancer & Oncology Authors: Tags: ORIGINAL ARTICLE Source Type: research
ConclusionsEndostar delivered by CIV with CCRT may be a better option than IV in terms of potential survival and safety for unresectable stage III NSCLC.Key pointsSignificant findings of the study Endostar delivered by continuous intravenous pumping might achieve more favorable survival over intravenous injection and reduce adverse hematological reactions in patients with unresectable stage III NSCLC treated with Endostar combined with CCRT.What this study adds The administration route of recombinant human endostatin is also one key factor for survival and safety to consider when treating patients with unresectable stage III NSCLC.
Source: Thoracic Cancer - Category: Cancer & Oncology Authors: Tags: ORIGINAL ARTICLE Source Type: research
ConclusionsThe use of osimertinib immediately after nivolumab significantly increased the frequency of grade 3 or higher hepatotoxicity in patients with advanced NSCLC harboringEGFR mutation acquired T790M resistance.
Source: Thoracic Cancer - Category: Cancer & Oncology Authors: Tags: ORIGINAL ARTICLE Source Type: research
Date: Tuesday, 04 21, 2020; Speaker: Kapil Bharti, Ph.D., Head of the Ocular and Stem Cell Translational Research Section , National Eye Institute; Building 10; Lipsett Amphitheatre ; Videocast Event
Source: NIH Calendar of Events - Category: American Health Source Type: events
To gain a better understanding of the factors that govern in vivo cellular recognition, artificial glycoproteins are created as biomimetic probes to study the influence of specific glycan assemblies to biodistribution. The principle aim of this Review is to present pioneering research that has driven artificial glycoprotein ‐based targeting and subsequent adaptations with potential therapeutic applications. AbstractAkin to a cellular “fingerprint,” the glycocalyx is a glycan‐enriched cellular coating that plays a crucial role in mediating cell‐to‐cell interactions. To gain a better understanding of the ...
Source: Small - Category: Nanotechnology Authors: Tags: Review Source Type: research
In this study, biogenic nanoparticles are obtained directly from lipoaspirate, an easily accessible and abundant source of biological material. Compared to ADSC‐EVs, lipoaspirate nanoparticles (Lipo‐NPs) take less time to process (hours compared to months) and cost less t o produce (clinical‐grade cell culture facilities are not required). The physicochemical characteristics and anti‐inflammatory properties of Lipo‐NPs are evaluated and compared to those of patient‐matched ADSC‐EVs. Moreover, guanabenz loading in Lipo‐NPs is evaluated for enhanced anti‐ inflammatory effects. Apolipoprotein E and glyceroli...
Source: Small - Category: Nanotechnology Authors: Tags: Full Paper Source Type: research
Alla S. Koltsova1,2, Anna A. Pendina1, Olga A. Efimova1*, Olga G. Chiryaeva1, Tatyana V. Kuznetzova1 and Vladislav S. Baranov1,2 1D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, Saint Petersburg, Russia 2Department of Genetics and Biotechnology, Saint Petersburg State University, Saint Petersburg, Russia In the present review, we focus on the phenomenon of chromothripsis, a new type of complex chromosomal rearrangements. We discuss the challenges of chromothripsis detection and its distinction from other chromoanagenesis events. Along with already known causes and mechanisms, we introdu...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
Successful use of immune checkpoint inhibitors in a variety of cancers has generated interest in using this approach in pediatric brain tumors. We performed a retrospective review of 10 consecutive children (6 boys, 4 girls; ages, 2 to 17 y), with recurrent or refractory pediatric brain tumors (5 high-grade glioma, 1 low-grade glioma, pineoblastoma, medulloblastoma, ependymoma, and CNS embryonal tumor, NOS) treated at Rady Children’s Hospital San Diego from 2015 to 2017 with the immune checkpoint inhibitor nivolumab (3 mg/kg every 2 wk). Eight of 10 patients received prior chemotherapy and 9 radi...
Source: Journal of Pediatric Hematology Oncology - Category: Hematology Tags: Online Articles: Original Articles Source Type: research
Purpose of review Brain tumors are the most common solid tumors and leading cause of cancer-related death in children. The advent of large-scale genomics has resulted in a plethora of profiling studies that have mapped the genetic and epigenetic landscapes of pediatric brain tumors, ringing in a new era of precision diagnostics and targeted therapies. In this review, we highlight the most recent findings, focusing on studies published after 2015, and discuss how new evidence is changing the care of children with brain tumors. Recent findings Genome-wide and epigenome-wide profiling data have revealed distinct tumor en...
Source: Current Opinion in Pediatrics - Category: Pediatrics Tags: HEMATOLOGY AND ONCOLOGY: Edited by Susan M. Blaney Source Type: research
Conclusions: Although brain tumors constituted 30% of all our solid tumors, only 56% of them received appropriate treatment and 25% abandoned treatment. High rates of abandonment were a consequence of late diagnosis, complex multidisciplinary treatment involved, high treatment cost, lack of uniformity in management between different oncology centers and poor prognosis of the tumor subtype.
Source: Journal of Pediatric Neurosciences - Category: Neuroscience Authors: Source Type: research
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