Abstract
Alterations of various signaling pathways implicated in cell survival or cell death may have relevance in cancer cell drug resistance. In particular, the EGF-R pathway may affect cellular response to platinum compounds, because these drugs are capable of modulating the signaling occurring through activation of EGF-R or EGF-R-mediated activation of downstream events. Recent evidence indicates that ovarian carcinoma cells selected for resistance to cisplatin and oxali-platin exhibits decreased sensitivity to gefitinib. The effect appears not dependent on failure to inhibit the target receptor, but is associated with increased phospho-ERK1/2 levels in the resistant variants. Cells resistant to gefitinib also exhibit reduced sensitivity to MEK1/2 inhibitors. The concomitant activation of distinct mitogen-activated protein kinases, i.e., ERK1/2 and p38 appears a relevant feature of cell resistance to cisplatin.
Thus, the development of resistance to platinum drugs is associated with multiple alterations including deregulation of survival pathways activated by EGF-R resulting in a reduced cellular response to gefitinib.
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Perego, P., Benedetti, V., Lanzi, C., Zunino, F. (2009). Modulation of Survival Pathways in Ovarian Carcinoma Cells Resistant to Platinum Compounds. In: Bonetti, A., Leone, R., Muggia, F.M., Howell, S.B. (eds) Platinum and Other Heavy Metal Compounds in Cancer Chemotherapy. Cancer Drug Discovery and Development. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60327-459-3_24
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