What hides behind the MASC: clinical response and acquired resistance to entrectinib after ETV6-NTRK3 identification in a mammary analogue secretory carcinoma (MASC)
2016; Elsevier BV; Volume: 27; Issue: 5 Linguagem: Inglês
10.1093/annonc/mdw042
ISSN1569-8041
AutoresAlexander Drilon, G. Li, Snjezana Doğan, Mrinal M. Gounder, Ronglai Shen, Maria E. Arcila, L. Wang, David M. Hyman, Jaclyn F. Hechtman, Wei Ge, Nicholas Cam, Jason Christiansen, Lu Wang, Edna Chow Maneval, Todd M. Bauer, Minesh Patel, Stephen V. Liu, S.-H.I. Ou, Anna F. Farago, Alice T. Shaw, Robert Shoemaker, J. K. Lim, Zachary Hornby, Pratik S. Multani, Marc Ladanyi, Manfred Berger, Nora Katabi, Ronald Ghossein, Alan L. Ho,
Tópico(s)Cancer Genomics and Diagnostics
ResumoBackgroundMammary 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 and methodsThis 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.ResultsA 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.ConclusionsThis 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).
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