NUT Carcinoma (NC) is a rare cancer that results from the formation of an oncogenic fusion protein between a general bromodomain gene on chromosome 19 with NUT, which typically is only involved in genes for testes, on chromosome 15, causing high levels of undifferentiated cells to develop into malignant tumors. The average patient prognosis is between 6-7 months with a 0% survival rate. In clinical applications, NC has a high chance of becoming resistant to treatments. Current clinical studies focus on the effects of single drugs on NC, yet there is more to be investigated for synergistic drug treatments. The purpose of this study is to investigate different drug combinations that could be of use clinically, as well as to create cell resistance in NC cell lines which will then be used to determine if resistant cells obtain collateral sensitivity or resistance to other chemotherapy drugs. Three separate cell lines (NC-14, NC-1015, and NC-690) directly derived from NC patients (gifted from Dr. Christopher French, Brigham and Women’s Hospital, Boston) were evaluated for initial sensitivity to different chemotherapeutic drugs via GI50 assays. Seven drugs were selected based on either clinical application in NC patients or use in cancers sharing similar mechanisms to NC including Mirdametinib, Molibresib, Venetoclax, Birabresib, ARV-771, (+)-JQ1, and Trametinib. Consistent results indicate that Mirdametinib, Trametinib, and Venetoclax do not appear to have an impact on any of the three NC cell lines. However, promising results for ARV-771, (+)-JQ1, and Birabresib for 1015 and 690 cell lines were obtained, with GI50 values for both cells lines in the low nM range for all three drugs. Current, ongoing experiments include growing resistant 1015 and 690 cell lines to ARV-771 and (+)-JQ1, respectively, by initially dosing cells with GI10 values from the collected data, as well as evaluating their sensitivity to combination treatments.
Support and funding provided by the Elon University Lumen Prize, the Elon University College Fellows Program, and the Elon University Undergraduate Research Program.
