TP53 and cancer: Among the mechanisms that result in increased levels of nuclear HSF1, in a broad range of cancers, include amplification of the HSF1 gene located within chromosome 8q24.3, reduced expression of the HSF1 degradation F box E3 ligase Fbxw7, activation by loss of p53 and increased HSF1 transcription by oncogenic signaling pathways such as NOTCH signaling30,80–82.