Innovative Therapeutic Strategies for Effective Treatment of Brain Metastases.
brain metastases
drug delivery
immunotherapy
nanomedicine
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
14 Mar 2019
14 Mar 2019
Historique:
received:
14
02
2019
revised:
08
03
2019
accepted:
09
03
2019
entrez:
17
3
2019
pubmed:
17
3
2019
medline:
17
7
2019
Statut:
epublish
Résumé
Brain metastases are the most prevalent of intracranial malignancies. They are associated with a very poor prognosis and near 100% mortality. This has been the case for decades, largely because we lack effective therapeutics to augment surgery and radiotherapy. Notwithstanding improvements in the precision and efficacy of these life-prolonging treatments, with no reliable options for adjunct systemic therapy, brain recurrences are virtually inevitable. The factors limiting intracranial efficacy of existing agents are both physiological and molecular in nature. For example, heterogeneous permeability, abnormal perfusion and high interstitial pressure oppose the conventional convective delivery of circulating drugs, thus new delivery strategies are needed to achieve uniform drug uptake at therapeutic concentrations. Brain metastases are also highly adapted to their microenvironment, with complex cross-talk between the tumor, the stroma and the neural compartments driving speciation and drug resistance. New strategies must account for resistance mechanisms that are frequently engaged in this milieu, such as HER3 and other receptor tyrosine kinases that become induced and activated in the brain microenvironment. Here, we discuss molecular and physiological factors that contribute to the recalcitrance of these tumors, and review emerging therapeutic strategies, including agents targeting the PI3K axis, immunotherapies, nanomedicines and MRI-guided focused ultrasound for externally controlling drug delivery.
Identifiants
pubmed: 30875730
pii: ijms20061280
doi: 10.3390/ijms20061280
pmc: PMC6471202
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
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