New treatments in advanced gastrointestinal stromal tumor.
Antineoplastic Agents
/ therapeutic use
Gastrointestinal Neoplasms
/ drug therapy
Gastrointestinal Stromal Tumors
/ drug therapy
Humans
Naphthyridines
/ therapeutic use
Protein Kinase Inhibitors
/ therapeutic use
Proto-Oncogene Proteins c-kit
/ genetics
Pyrazoles
/ therapeutic use
Pyrroles
/ therapeutic use
Receptor, Platelet-Derived Growth Factor alpha
/ genetics
Triazines
/ therapeutic use
Urea
/ analogs & derivatives
Journal
Current opinion in oncology
ISSN: 1531-703X
Titre abrégé: Curr Opin Oncol
Pays: United States
ID NLM: 9007265
Informations de publication
Date de publication:
01 07 2021
01 07 2021
Historique:
pubmed:
20
4
2021
medline:
28
8
2021
entrez:
19
4
2021
Statut:
ppublish
Résumé
The current article revisits the most recent advances that occurred in the field of gastrointestinal stromal tumor (GIST) therapeutics. GIST is driven by the oncogenic activation of KIT or PDGFRA receptor tyrosine kinases, and agents targeting these receptors lead to substantial benefit throughout the entire course of the disease. Two new drugs were approved in 2020. On one hand, ripretinib obtained the regulatory approval for the treatment of GIST patients after progression to all standard treatments. On the other hand, avapritinib became the first agent ever displaying activity in GIST driven by the multiresistant PDGFRA D842V mutation. The addition of both drugs to GIST therapeutics constitutes a remarkable milestone, particularly considering that the last agent approved was back in 2012. Similarly, the recent identification of neurotrophic tyrosine receptor kinase (NTRK) fusions in a subset of KIT/PDGFRA wild-type GISTs led to an open window for tailored treatment using specific NTRK inhibitors. Finally, multiple efforts have been made toward the clinical implementation of circulating tumor DNA evaluation to guide clinical decisions in GIST. GIST has been consolidated over the years as a paradigmatic model in personalized medicine for the successful development of novel therapeutic strategies through targeted inhibition of oncogenic drivers.
Identifiants
pubmed: 33867479
doi: 10.1097/CCO.0000000000000745
pii: 00001622-202107000-00012
doi:
Substances chimiques
Antineoplastic Agents
0
Naphthyridines
0
Protein Kinase Inhibitors
0
Pyrazoles
0
Pyrroles
0
Triazines
0
avapritinib
513P80B4YJ
Urea
8W8T17847W
ripretinib
9XW757O13D
KIT protein, human
EC 2.7.10.1
Proto-Oncogene Proteins c-kit
EC 2.7.10.1
Receptor, Platelet-Derived Growth Factor alpha
EC 2.7.10.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
323-328Informations de copyright
Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
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