Published January 1, 2020
| Version v1
Journal article
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Predictive Gene Signature for Pyrazolopyrimidine Derivative c-Src Inhibitor 10a Sensitivity in Melanoma Cells
Creators
- 1. Bilkent Univ, Dept Mol Biol & Genet, TR-06800 Ankara, Turkey
- 2. Lokman Hekim Univ, Fac Med, Dept Med Microbiol, TR-06510 Ankara, Turkey
- 3. Univ Siena, Dept Excellence 2018 2022, Dept Biotechnol Chem & Pharm, I-53100 Siena, Italy
- 4. Zonguldak Bulent Ecevit Univ, Dept Mol Biol & Genet, TR-67100 Zonguldak, Turkey
- 5. Hadassah Hebrew Univ Hosp, Sharett Inst Oncol, IL-91120 Jerusalem, Israel
Description
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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