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Ex vivo assessment of targeted therapies in a rare metastatic epithelial-myoepithelial carcinoma.
- Source :
-
Neoplasia (New York, N.Y.) [Neoplasia] 2020 Sep; Vol. 22 (9), pp. 390-398. Date of Electronic Publication: 2020 Jul 06. - Publication Year :
- 2020
-
Abstract
- Epithelial-myoepithelial carcinoma (EMC) is a rare subtype of salivary gland neoplasms. Since the initial description of the cancer, just over 300 cases have been reported. EMCs occupy a biphasic cellular differentiation-state defined by the constitution of two cell types representing epithelial and myoepithelial lineages, yet the functional consequence of the differentiation-state heterogeneity with respect to therapy resistance of the tumors remains unclear. The reported local recurrence rate of the cases is approximately 30%, and while distant metastases are rare, a significant fraction of these cases are reported to receive no survival benefit from radio- or chemotherapy given in addition to surgery. Moreover, no targeted therapies have been reported for these neoplasms. We report here the first use and application of ex vivo drug screening together with next generation sequencing to assess targeted treatment strategies for a rare metastatic epithelial-myoepithelial carcinoma. Results of the ex vivo drug screen demonstrate significant differential therapeutic sensitivity between the epithelial and myoepithelial intra-tumor cell lineages suggesting that differentiation-state heterogeneity within epithelial-myoepithelial carcinomas may present an outlet to partial therapeutic responses to targeted therapies including MEK and mTOR inhibitors. These results suggest that the intra-tumor lineage composition of EMC could be an important factor to be assessed when novel treatments are being evaluated for management of metastatic EMC.<br /> (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Adult
Antineoplastic Agents therapeutic use
Biomarkers, Tumor genetics
Carcinoma drug therapy
Carcinoma genetics
Carcinoma pathology
DNA Mutational Analysis
Female
Gene Expression Profiling
High-Throughput Screening Assays
Humans
Lung Neoplasms genetics
Lung Neoplasms secondary
Myoepithelioma genetics
Myoepithelioma pathology
Prognosis
Salivary Gland Neoplasms genetics
Salivary Gland Neoplasms pathology
Tumor Cells, Cultured
Biomarkers, Tumor antagonists & inhibitors
Everolimus therapeutic use
Lung Neoplasms drug therapy
Molecular Targeted Therapy
Mutation
Myoepithelioma drug therapy
Salivary Gland Neoplasms drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1476-5586
- Volume :
- 22
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Neoplasia (New York, N.Y.)
- Publication Type :
- Academic Journal
- Accession number :
- 32645560
- Full Text :
- https://doi.org/10.1016/j.neo.2020.06.007