Building on our recent finding that HSF1 activity is effectively suppressed by wtp53 via a p53 - CDKN1A/p21 - CDK4/6 - MAPK axis [36], we tested the hypothesis that p53 activation (in case of wtp53, inducing CDKN1A/p21 upregulation) or direct CDK4/6-based cell cycle inhibition (in case of mutp53) provide new opportunities for improving the efficacy of HSP90-based therapy of CRC. Here, HSP90AA1 is linked to colorectal carcinoma.