Excellent Response to MEK Inhibition in an
Carcinoma
/ drug therapy
Enzyme Inhibitors
/ therapeutic use
Female
Humans
Middle Aged
Mitogen-Activated Protein Kinase Kinases
/ antagonists & inhibitors
Mutation
Myoepithelioma
/ drug therapy
Oncogene Proteins, Fusion
/ genetics
Phosphotransferases (Alcohol Group Acceptor)
/ genetics
Protein Kinase Inhibitors
/ therapeutic use
Proto-Oncogene Proteins B-raf
/ genetics
Soft Tissue Neoplasms
/ drug therapy
AGK-BRAF gene fusion
MEK-inhibitor
NGS
cobimetinib
myoepithelial carcinoma
next generation sequencing
Journal
Anticancer research
ISSN: 1791-7530
Titre abrégé: Anticancer Res
Pays: Greece
ID NLM: 8102988
Informations de publication
Date de publication:
Jan 2022
Jan 2022
Historique:
received:
12
11
2021
revised:
30
11
2021
accepted:
02
12
2021
entrez:
31
12
2021
pubmed:
1
1
2022
medline:
13
1
2022
Statut:
ppublish
Résumé
Soft tissue myoepithelial carcinomas (STMC) are a rare, malignant subgroup of myoepithelial tumors that arise typically in glandular or ductal tissues, but also in the bone and soft and cutaneous tissues. Due to its rarity, there is no consensus regarding the treatment of STMC, including chemotherapy or other systemic agents for metastatic STMC. A chemotherapy- and regorafenib-refractory STMC, harboring an AGK-BRAF fusion, was successfully treated using MEK-inhibition with cobimetinib in monotherapy. MEK-inhibition with cobimetinib effectively silenced paradoxical MAP kinase/ERK-signaling pathway activation after regorafenib monotherapy, and resulted in a significant and durable clinical response. This effect of MEK-inhibition in STMC harboring an AGK-BRAF fusion has not been previously reported and contributes to the existing, yet limited, knowledge on the treatment of BRAF fusion-driven tumors. Also, our case highlights the importance of next generation sequencing in driving further rational therapeutic choices to provide disease control and palliation.
Sections du résumé
BACKGROUND
BACKGROUND
Soft tissue myoepithelial carcinomas (STMC) are a rare, malignant subgroup of myoepithelial tumors that arise typically in glandular or ductal tissues, but also in the bone and soft and cutaneous tissues. Due to its rarity, there is no consensus regarding the treatment of STMC, including chemotherapy or other systemic agents for metastatic STMC.
CASE REPORT
METHODS
A chemotherapy- and regorafenib-refractory STMC, harboring an AGK-BRAF fusion, was successfully treated using MEK-inhibition with cobimetinib in monotherapy. MEK-inhibition with cobimetinib effectively silenced paradoxical MAP kinase/ERK-signaling pathway activation after regorafenib monotherapy, and resulted in a significant and durable clinical response.
CONCLUSION
CONCLUSIONS
This effect of MEK-inhibition in STMC harboring an AGK-BRAF fusion has not been previously reported and contributes to the existing, yet limited, knowledge on the treatment of BRAF fusion-driven tumors. Also, our case highlights the importance of next generation sequencing in driving further rational therapeutic choices to provide disease control and palliation.
Identifiants
pubmed: 34969747
pii: 42/1/373
doi: 10.21873/anticanres.15495
doi:
Substances chimiques
Enzyme Inhibitors
0
Oncogene Proteins, Fusion
0
Protein Kinase Inhibitors
0
AGK protein, human
EC 2.7.1.-
Phosphotransferases (Alcohol Group Acceptor)
EC 2.7.1.-
BRAF protein, human
EC 2.7.11.1
Proto-Oncogene Proteins B-raf
EC 2.7.11.1
Mitogen-Activated Protein Kinase Kinases
EC 2.7.12.2
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
373-379Informations de copyright
Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.