Entrectinib and other ALK/TRK inhibitors for the treatment of neuroblastoma.

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Pacenta HL, Macy ME

Entrectinib and other ALK/TRK inhibitors for the treatment of neuroblastoma.

Drug Des Devel Ther. 2018 Oct 23;12:3549-3561. doi: 10.2147/DDDT.S147384. eCollection 2018.

PubMed ID
30425456 [ View in PubMed
]
Abstract

RTK plays important roles in many cellular signaling processes involved in cancer growth and development. ALK, TRKA, TRKB, TRKC, and ROS1 are RTKs involved in several canonical pathways related to oncogenesis. These proteins can be genetically altered in malignancies, leading to receptor activation and constitutive signaling through their respective downstream pathways. Neuroblastoma (NB) is the most common extracranial solid tumor in childhood, and despite intensive therapy, there is a high mortality rate in cases with a high-risk disease. Alterations of ALK and differential expression of TRK proteins are reported in a proportion of NB. Several inhibitors of ALK or TRKA/B/C have been evaluated both preclinically and clinically in the treatment of NB. These agents have had variable success and are not routinely used in the treatment of NB. Entrectinib (RXDX-101) is a pan-ALK, TRKA, TRKB, TRKC, and ROS1 inhibitor with activity against tumors with ALK, NTRK1, NTRK2, NTRK3, and ROS1 alterations in Phase I clinical trials in adults. Entrectinib's activity against both ALK and TRK proteins suggests a possible role in NB treatment, and it is currently under investigation in both pediatric and adult oncology patients.

DrugBank Data that Cites this Article

Drugs
Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
EntrectinibBDNF/NT-3 growth factors receptorProteinHumans
Unknown
Inhibitor
Details
EntrectinibHigh affinity nerve growth factor receptorProteinHumans
Yes
Inhibitor
Details
EntrectinibNT-3 growth factor receptorProteinHumans
Yes
Inhibitor
Details
EntrectinibProto-oncogene tyrosine-protein kinase ROSProteinHumans
Yes
Inhibitor
Details