entrectinib and Salivary-Gland-Neoplasms

entrectinib has been researched along with Salivary-Gland-Neoplasms* in 3 studies

Other Studies

3 other study(ies) available for entrectinib and Salivary-Gland-Neoplasms

ArticleYear
Clinicopathological investigation of secretory carcinoma cases including a successful treatment outcome using entrectinib for high-grade transformation: a case report.
    BMC medical genomics, 2022, 01-06, Volume: 15, Issue:1

    Secretory carcinoma (SC) of the salivary gland is a recently described malignant tumor harboring characteristic ETV6-NTRK3 gene fusion. SC generally has a favorable clinical course, and is currently regarded as a low-grade carcinoma. However, a small subset of SCs demonstrates aggressive clinical features with histologically high-grade transformed morphology, the molecular pathogenesis of which has not yet been elucidated. In this study, we performed a clinicopathological and molecular genetic study of patients with SC of the head and neck displaying various clinical characteristics to investigate the differences of pathological and molecular genetics between low-grade and high-grade components of SC.. Three cases with SC of the head and neck, including a conventional low-grade SC and two high-grade transformed SCs are described. High-grade transformed SCs with histological features such as nuclear polymorphism, distinctive nucleoli and increased mitotic activity developed locoregional recurrence and distant metastasis. Immunohistochemical analysis revealed that low- and high-grade components showed different expression patterns for S-100 protein and mammaglobin, whereas all examined components were positive for p-STAT5. p53-positive cell population was markedly higher in one case with high-grade transformed SC. The proliferative activity of high-grade components was markedly increased, with the Ki-67 labeling index ranging up to 30-32%. A fluorescence in situ hybridization study with an ETV6 (12p13) break apart probe revealed split signals in the nuclei in all 3 cases. A targeted next-generation sequencing-based fusion assay demonstrated that all 6 clinical samples from the 3 patients showed the presence of the ETV6-NTRK3 fusion transcripts. One patient with high-grade transformed SC showed a dramatic clinical response to the pan-TRK inhibitor, entrectinib, for the treatment of locoregional recurrence and pulmonary metastasis.. High-grade transformed SC showed aggressive clinical and pathological features with increased Ki-67 labeling index. Molecular genetic study of gene rearrangement appears to be beneficial treatment as the presence of ETV6-NTRK3 translocation may represent a therapeutic target in SC, particularly the high-grade transformed type.

    Topics: Benzamides; Biomarkers, Tumor; Carcinoma; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Indazoles; Neoplasm Recurrence, Local; Oncogene Proteins, Fusion; Salivary Gland Neoplasms; Treatment Outcome

2022
Clinical Activity of Selitrectinib in a Patient With Mammary Analogue Secretory Carcinoma of the Parotid Gland With Secondary Resistance to Entrectinib.
    Journal of the National Comprehensive Cancer Network : JNCCN, 2021, Volume: 19, Issue:5

    NTRK gene fusions are found in <1% of all cancers but are uniformly present in mammary analog secretory carcinomas (MASC) of the salivary glands. Two selective histology-agnostic tropomyosin receptor kinase (TRK) inhibitors are currently approved for malignancies with these oncogenic fusions. Resistance to TRK inhibition has been recognized, and the mediating mechanisms are presently being studied. This report describes a patient diagnosed with an MASC of the parotid gland who after undergoing multiple lines of treatment was found to have an ETV6-NTRK3 fusion and initiated TRK-targeted therapy using entrectinib. Upon disease progression, we performed tumor genetic sequencing that showed a secondary resistance mutation. The patient subsequently responded to selitrectinib, a next-generation TRK inhibitor.

    Topics: Aza Compounds; Benzamides; Drug Resistance, Neoplasm; Humans; Indazoles; Mammary Analogue Secretory Carcinoma; Oncogene Proteins, Fusion; Parotid Gland; Protein Kinase Inhibitors; Salivary Gland Neoplasms

2021
What hides behind the MASC: clinical response and acquired resistance to entrectinib after ETV6-NTRK3 identification in a mammary analogue secretory carcinoma (MASC).
    Annals of oncology : official journal of the European Society for Medical Oncology, 2016, Volume: 27, Issue:5

    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.. 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.. 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.. 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).

    Topics: Adult; Benzamides; Biomarkers, Tumor; Carcinoma, Acinar Cell; Clinical Trials as Topic; Crizotinib; Diagnosis, Differential; Drug Resistance, Neoplasm; Female; Humans; In Situ Hybridization, Fluorescence; Indazoles; Mammary Analogue Secretory Carcinoma; Mutation; Oncogene Proteins, Fusion; Pyrazoles; Pyridines; Salivary Gland Neoplasms

2016
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