Melanoma in general is quite resistant to killing by cytotoxic chemotherapy and conventional doses of radiation. These clinical observations suggest that mechanisms of resistance to cell death are likely highly active in this tumor type. Several observations in our gene expression profiling experiment support this contention. Highly expressed in many melanoma tumors was the gene encoding anti-apoptotic protein survivin, which has been shown to be correlated with poor clinical outcome in other series . Many melanoma tumors were found to overexpress the Notch transcriptional target Heyl, arguing that Notch signaling is constitutive in those tumors. Notch signaling has been shown to support survival of melanoma tumor cells in vitro, with inhibition of Notch processing leading to melanoma cell apoptosis . An additional factor found to be overexpressed was the serine protease inhibitor SerpinA3. Molecules in the Serpin family have been shown to mediate resistance of target cells to granule-mediated lysis by T cells . Thus, elevated expression of survivin, active Notch, and serine protease inhibitors in fresh melanoma biopsies points towards specific anti-apoptotic factors to focus upon in future studies. These tumor cell-intrinsic survival mechanisms are depicted in Figure 4.3.
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Complete Guide to Preventing Skin Cancer. We all know enough to fear the name, just as we do the words tumor and malignant. But apart from that, most of us know very little at all about cancer, especially skin cancer in itself. If I were to ask you to tell me about skin cancer right now, what would you say? Apart from the fact that its a cancer on the skin, that is.