Repurposing Tyrosine Kinase Inhibitors to Overcome Multidrug Resistance in Cancer: A Focus on Transporters and Lysosomal Sequestration.
ATP-Binding Cassette Transporters
/ genetics
Animals
Biological Transport
Clinical Trials as Topic
Drug Repositioning
Drug Resistance, Multiple
/ drug effects
Drug Resistance, Neoplasm
/ drug effects
Humans
Lysosomes
/ drug effects
Membrane Transport Proteins
/ genetics
Neoplasms
/ drug therapy
Protein Kinase Inhibitors
/ pharmacology
Solute Carrier Proteins
/ genetics
Treatment Outcome
ABC transporter
SLC transporter
cancer
lysosomal sequestration
multidrug resistance
tyrosine kinase inhibitor
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:
30 Apr 2020
30 Apr 2020
Historique:
received:
08
04
2020
revised:
26
04
2020
accepted:
27
04
2020
entrez:
6
5
2020
pubmed:
6
5
2020
medline:
12
2
2021
Statut:
epublish
Résumé
Tyrosine kinase inhibitors (TKIs) are being increasingly used to treat various malignancies. Although they were designed to target aberrant tyrosine kinases, they are also intimately linked with the mechanisms of multidrug resistance (MDR) in cancer cells. MDR-related solute carrier (SLC) and ATB-binding cassette (ABC) transporters are responsible for TKI uptake and efflux, respectively. However, the role of TKIs appears to be dual because they can act as substrates and/or inhibitors of these transporters. In addition, several TKIs have been identified to be sequestered into lysosomes either due to their physiochemical properties or via ABC transporters expressed on the lysosomal membrane. Since the development of MDR represents a great concern in anticancer treatment, it is important to elucidate the interactions of TKIs with MDR-related transporters as well as to improve the properties that would prevent TKIs from diffusing into lysosomes. These findings not only help to avoid MDR, but also help to define the possible impact of combining TKIs with other anticancer drugs, leading to more efficient therapy and fewer adverse effects in patients.
Identifiants
pubmed: 32365759
pii: ijms21093157
doi: 10.3390/ijms21093157
pmc: PMC7247577
pii:
doi:
Substances chimiques
ATP-Binding Cassette Transporters
0
Membrane Transport Proteins
0
Protein Kinase Inhibitors
0
Solute Carrier Proteins
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Ministry of Healthcare of the Czech Republic
ID : 17-33104A
Organisme : National Program of Sustainability II (MEYS CR)
ID : LQ1605
Organisme : JCMM
ID : Brno Ph.D. Talent 2017
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