Drug delivery across the blood-brain barrier for the treatment of pediatric brain tumors – An update

Power, Erica A; Rechberger, Julian S.; Gupta, Sumit; Schwartz, Jonathan D.; Daniels, David J.; Khatua, Soumen

doi:10.1016/j.addr.2022.114303

Cited by 28 publications

(15 citation statements)

References 191 publications

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“…Tumor location, presence of BBB, infiltrative nature, molecular, genetic, and phenotypic heterogeneity, and resistance to chemotherapy, make GBM very difficult to treat [ 77 ]. Prognosis and survival of gliomas directly correlates with the ability to be resected surgically [ 166 ]. However, complete surgical resection of glioblastomas is not attainable because it is infiltrating and grows into the normal brain tissues.…”

Section: Discussionmentioning

confidence: 99%

Tyrosine Kinase Inhibitors for Glioblastoma Multiforme: Challenges and Opportunities for Drug Delivery

Brar

Jose

et al. 2022

Pharmaceutics

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Glioblastoma multiforme (GBM) is an aggressive brain tumor with high mortality rates. Due to its invasiveness, heterogeneity, and incomplete resection, the treatment is very challenging. Targeted therapies such as tyrosine kinase inhibitors (TKIs) have great potential for GBM treatment, however, their efficacy is primarily limited by poor brain distribution due to the presence of the blood–brain barrier (BBB). This review focuses on the potential of TKIs in GBM therapy and provides an insight into the reasons behind unsuccessful clinical trials of TKIs in GBM despite the success in treating other cancer types. The main section is dedicated to the use of promising drug delivery strategies for targeted delivery to brain tumors. Use of brain targeted delivery strategies can help enhance the efficacy of TKIs in GBM. Among various drug delivery approaches used to bypass or cross BBB, utilizing nanocarriers is a promising strategy to augment the pharmacokinetic properties of TKIs and overcome their limitations. This is because of their advantages such as the ability to cross BBB, chemical stabilization of drug in circulation, passive or active targeting of tumor, modulation of drug release from the carrier, and the possibility to be delivered via non-invasive intranasal route.

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Section: Discussionmentioning

confidence: 99%

Tyrosine Kinase Inhibitors for Glioblastoma Multiforme: Challenges and Opportunities for Drug Delivery

Brar

Jose

et al. 2022

Pharmaceutics

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“…To efficiently release drugs into the brain, various strategies have been developed. These include chemical modifications of drug and prodrugs, temporary disruption of tight junctions, and local delivery into the brain by neurosurgery. , However, the temporary disruption of the BBB is risky and can cause an uncontrolled influx of molecules into the CNS. Therefore, the ideal method to transport drugs across the BBB should be controlled and not damage the barrier.…”

Section: Phase I: Nanomedicine Biodistribution and Clearancementioning

confidence: 99%

A Nanomedicine Structure–Activity Framework for Research, Development, and Regulation of Future Cancer Therapies

et al. 2022

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Despite their clinical success in drug delivery applications, the potential of theranostic nanomedicines is hampered by mechanistic uncertainty and a lack of scienceinformed regulatory guidance. Both the therapeutic efficacy and the toxicity of nanoformulations are tightly controlled by the complex interplay of the nanoparticle's physicochemical properties and the individual patient/tumor biology; however, it can be difficult to correlate such information with observed outcomes. Additionally, as nanomedicine research attempts to gradually move away from large-scale animal testing, the need for computer-assisted solutions for evaluation will increase. Such models will depend on a clear understanding of structure− activity relationships. This review provides a comprehensive overview of the field of cancer nanomedicine and provides a knowledge framework and foundational interaction maps that can facilitate future research, assessments, and regulation. By forming three complementary maps profiling nanobio interactions and pathways at different levels of biological complexity, a clear picture of a nanoparticle's journey through the body and the therapeutic and adverse consequences of each potential interaction are presented.

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“…Children with brain cancer (e.g., medulloblastoma) were more frequently studied than other solid tumors, likely due the higher prevalence rates and high levels of treatment complications and long-term impairments ( 13 ). Challenges in crossing the blood-brain barrier mean that treatment for CNS tumors differ to that of other solid tumors, with brain cancer treated with more surgery and radiation-focused treatments compared to other solid tumors, which are more often treated with a rigorous regimen of surgery and chemotherapy ( 56 , 57 ). Children with bone tumors in particular, (e.g., osteosarcoma) have their own unique experiences and needs, often effected by amputations, disability and poorer QoL ( 7 , 58 ).…”

Section: Discussionmentioning

confidence: 99%

Therapeutic exercise interventions in pediatric survivors of brain cancer and other solid tumors: A scoping review

et al. 2022

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BackgroundImproved survival rates for children with solid tumors presents an ongoing challenge of how to maximize quality of survivorship and effectively manage the short- and long-term complications of disease and treatment. To gain an understanding of the extent and nature of research pertaining to therapeutic exercise interventions and identify knowledge gaps, we conducted a scoping review of exercise training studies conducted in pediatric survivors of brain cancer and other solid tumors.MethodA systematic literature search was performed across four electronic databases. Papers were selected for full-text review if they included participants treated for brain cancer or other solid tumors, with at least 50% of participants aged ≤ 21 years, evaluated an exercise intervention ≥2-weeks in duration, and were published in an English, peer-reviewed journal. We included the following quantitative study designs; randomized controlled trials, non-randomized trials, and single-arm pre-test-post-test.ResultsOf the 7,482 citations identified, 17 papers met the inclusion criteria (presenting findings from eleven studies). Two studies were randomized controlled trials, five studies were non-randomized controlled trials, and four studies were a single-arm pre-test post-test design. Average age of participants ranged from 7.3–15.5 years, and time since diagnosis ranged from 3 to 70 months. Five studies included participants with brain tumors exclusively, three studies included other solid tumors, and three studies included a mixed sample (brain and other solid tumors). A wide range of exercise modalities were employed, including cycle ergometry, resistance training, sport, yoga, and active gaming. The length of the exercise program ranged from 3–40 weeks and frequency from 3–11 sessions per week. Exercise session duration ranged from 15–180 min, with most studies reporting 30–90-min sessions. Adherence ranged from 77 to 100%, with none of the studies reporting adverse events. Studies reported improvements in cardiorespiratory fitness, functional strength, physical activity, and quality of life.ConclusionsA small number of mostly low methodological quality studies have examined the effects of therapeutic exercise in pediatric survivors of solid tumors. Although limited, the extant literature supports the feasibility and safety of therapeutic exercise interventions for pediatric survivors of brain cancer and other solid tumors.

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Drug delivery across the blood-brain barrier for the treatment of pediatric brain tumors – An update

Cited by 28 publications

References 191 publications

Tyrosine Kinase Inhibitors for Glioblastoma Multiforme: Challenges and Opportunities for Drug Delivery

Tyrosine Kinase Inhibitors for Glioblastoma Multiforme: Challenges and Opportunities for Drug Delivery

A Nanomedicine Structure–Activity Framework for Research, Development, and Regulation of Future Cancer Therapies

Therapeutic exercise interventions in pediatric survivors of brain cancer and other solid tumors: A scoping review

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