학술논문

Childhood Brain Tumors: A Review of Strategies to Translate CNS Drug Delivery to Clinical Trials
Document Type
article
Source
Cancers, Vol 15, Iss 3, p 857 (2023)
Subject
drug delivery
blood–brain barrier
brain tumor model
preclinical
xenograft
companion animal
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Language
English
ISSN
15030857
2072-6694
Abstract
Brain and spinal tumors affect 1 in 1000 people by 25 years of age, and have diverse histological, biological, anatomical and dissemination characteristics. A mortality of 30–40% means the majority are cured, although two-thirds have life-long disability, linked to accumulated brain injury that is acquired prior to diagnosis, and after surgery or chemo-radiotherapy. Only four drugs have been licensed globally for brain tumors in 40 years and only one for children. Most new cancer drugs in clinical trials do not cross the blood–brain barrier (BBB). Techniques to enhance brain tumor drug delivery are explored in this review, and cover those that augment penetration of the BBB, and those that bypass the BBB. Developing appropriate delivery techniques could improve patient outcomes by ensuring efficacious drug exposure to tumors (including those that are drug-resistant), reducing systemic toxicities and targeting leptomeningeal metastases. Together, this drug delivery strategy seeks to enhance the efficacy of new drugs and enable re-evaluation of existing drugs that might have previously failed because of inadequate delivery. A literature review of repurposed drugs is reported, and a range of preclinical brain tumor models available for translational development are explored.