Predictive Gene Signature for Pyrazolopyrimidine Derivative c-Src Inhibitor 10a Sensitivity in Melanoma Cells
Date
2020Author
Kucukkaraduman, Baris and Turk, Can and Fallacara, Anna L. and Isbilen,
Murat and Senses, Kerem M. and Ayyildiz, Zeynep O. and Akbar, Muhammad
W. and Lotem, Michal and Botta, Maurizio and Gure, Ali O.
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Show full item recordAbstract
Melanoma is a highly aggressive cancer with poor prognosis. Although
more than 80\% of melanomas harbor an activating mutation in genes
within the MAPK pathway, which are mutually exclusive, usefulness of
therapies targeting MAPK pathway are impeded by innate and/or acquired
resistance in most patients. In this study, using melanoma cells, we
report the efficacy of a recently developed pyrazolo{[}3,4-d]pyrimidine
derived c-Src inhibitor 10a and identify a molecular signature which is
predictive of 10a chemosensitivity. We show that the expression of
TMED7, PLOD2, XRCCS, and NSUNS are candidate biomarkers for 10a
sensitivity. Although an undifferentiated/mesenchymal/invasive status of
melanoma cells is associated with resistance to 10a, we show here for
the first time that melanoma cells can be sensitized to 10a via
treatment with valproic acid, a histone deacetylase inhibitor.
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