TP53 and melanoma: Thus, altogether, direct MAPK inhibition by vemurafenib, indirect PI3K/AKT downregulation by PRIMA-1Met [36], and the supplemental effect by RT and PRIMA-1Met on p53 activation may explain the observed synergistic effect of the triplet BRAF inhibitor, p53 reactivator, and RT on BRAF mutant melanoma cells both in vitro and in vivo.