What hides behind the MASC: clinical response and acquired resistance to entrectinib after ETV6-NTRK3 identification in a mammary analogue secretory carcinoma (MASC).
Ann Oncol
; 27(5): 920-6, 2016 05.
Article
em En
| MEDLINE
| ID: mdl-26884591
ABSTRACT
BACKGROUND:
Mammary analogue secretory carcinoma (MASC) is a recently described pathologic entity. We report the case of a patient with an initial diagnosis of salivary acinic cell carcinoma later reclassified as MASC after next-generation sequencing revealed an ETV6-NTRK3 fusion. PATIENTS ANDMETHODS:
This alteration was targeted with the pan-Trk inhibitor entrectinib (Ignyta), which possesses potent in vitro activity against cell lines containing various NTRK1/2/3 fusions.RESULTS:
A dramatic and durable response was achieved with entrectinib in this patient, followed by acquired resistance that correlated with the appearance of a novel NTRK3 G623R mutation. Structural modeling predicts that this alteration sterically interferes with drug binding, correlating to decreased sensitivity to drug inhibition observed in cell-based assays.CONCLUSIONS:
This first report of clinical activity with TrkC inhibition and the development of acquired resistance in an NTRK3-rearranged cancer emphasize the utility of comprehensive molecular profiling and targeted therapy for rare malignancies (NCT02097810).Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Benzamidas
/
Neoplasias das Glândulas Salivares
/
Proteínas de Fusão Oncogênica
/
Carcinoma de Células Acinares
/
Carcinoma Secretor Análogo ao Mamário
/
Indazóis
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Adult
/
Female
/
Humans
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article