24 research outputs found
Ex vivo assessment of targeted therapies in a rare metastatic epithelial–myoepithelial carcinoma
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
Inactivation of FBXW7/hCDC4-β expression by promoter hypermethylation is associated with favorable prognosis in primary breast cancer
Targeting SOX9 for degradation to inhibit chemoresistance, metastatic spread, and recurrence
Cancer cells with stem-like properties are believed to contribute to treatment resistance, dissemination, and recurrence. SOX9 controls stem cell plasticity and its deregulation may provide a basis for tumor progression. Here, we summarize our findings of targeted SOX9 destruction by SCFFBW7 (Skp1/Cul1/F-box) in medulloblastoma and its potential for therapeutic intervention
Interferon α down-regulates telomerase reverse transcriptase and telomerase activity in human malignant and nonmalignant hematopoietic cells
Disruption of a novel Ectodermal Neural Cortex 1 antisense gene, ENC- 1AS and identification of ENC-1 overexpression in hairy cell leukemia
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