Molecular Medicine Israel

A Designed Inhibitor of p53 Aggregation Rescues p53 Tumor Suppression in Ovarian Carcinomas


  • We designed the peptide ReACp53 to halt aggregation of p53 in cells
  • ReACp53 rescues p53 transcription of target genes and restores apoptosis
  • In vivo ReACp53 halts progression and shrinks tumors bearing aggregation-prone p53
  • p53 aggregation in cancer is a target for therapy with ReACp53 as a lead compound


Half of all human cancers lose p53 function by missense mutations, with an unknown fraction of these containing p53 in a self-aggregated amyloid-like state. Here we show that a cell-penetrating peptide, ReACp53, designed to inhibit p53 amyloid formation, rescues p53 function in cancer cell lines and in organoids derived from high-grade serous ovarian carcinomas (HGSOC), an aggressive cancer characterized by ubiquitous p53 mutations. Rescued p53 behaves similarly to its wild-type counterpart in regulating target genes, reducing cell proliferation and increasing cell death. Intraperitoneal administration decreases tumor proliferation and shrinks xenografts in vivo. Our data show the effectiveness of targeting a specific aggregation defect of p53 and its potential applicability to HGSOCs.

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