TP53 and melanoma: On the other end of the spectrum, several decreased curvature pathways have been implicated with tumor-suppressor involvement in melanoma and, such as PAK degradation, where PAK is a known driver of drug resistance in melanoma, and several other tumor-suppressive pathways including p53 and DNA damage response pathways (which were also significantly enriched but not shown in top 10, see Supplementary Table S2)61,62.