TY - JOUR
T1 - Entrectinib and other ALK/TRK inhibitors for the treatment of neuroblastoma
AU - Pacenta, Holly L.
AU - Macy, Margaret E.
N1 - Publisher Copyright:
© 2018 Pacenta and Macy.
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
KW - ALK
KW - Neuroblastoma
KW - ROS1
KW - TRK
KW - entrectinib
UR - http://www.scopus.com/inward/record.url?scp=85056527131&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85056527131&partnerID=8YFLogxK
U2 - 10.2147/DDDT.S147384
DO - 10.2147/DDDT.S147384
M3 - Review article
C2 - 30425456
AN - SCOPUS:85056527131
SN - 1177-8881
VL - 12
SP - 3549
EP - 3561
JO - Drug Design, Development and Therapy
JF - Drug Design, Development and Therapy
ER -