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.
journal_name
Neoplasiajournal_title
Neoplasia (New York, N.Y.)authors
Mäkelä R,Arjonen A,Suryo Rahmanto A,Härmä V,Lehtiö J,Kuopio T,Helleday T,Sangfelt O,Kononen J,Rantala JKdoi
10.1016/j.neo.2020.06.007subject
Has Abstractpub_date
2020-09-01 00:00:00pages
390-398issue
9eissn
1522-8002issn
1476-5586pii
S1476-5586(20)30129-9journal_volume
22pub_type
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