Mechanistically, inhibition of CDK4/6 by Palbociclib under HSP90 inhibition again repressed HSF1 target genes (Figs. 6A and S6A, B) and lowered the levels of activated pSer326-HSF1 (Fig. 6B) in p53-proficient human CRC cells. This evidence concerns the gene TP53 and colorectal carcinoma.