Advanced Strategies for Therapeutic Targeting of Wild-Type and Mutant p53 in Cancer

Biomolecules. 2022 Apr 6;12(4):548. doi: 10.3390/biom12040548.


TP53 is a tumor suppressor gene that encodes a sequence-specific DNA-binding transcription factor activated by stressful stimuli; it upregulates target genes involved in growth suppression, cell death, DNA repair, metabolism, among others. TP53 is the most frequently mutated gene in tumors, with mutations not only leading to loss-of-function (LOF), but also gain-of-function (GOF) that promotes tumor progression, and metastasis. The tumor-specific status of mutant p53 protein has suggested it is a promising target for cancer therapy. We summarize the current progress of targeting wild-type and mutant p53 for cancer therapy through biotherapeutic and biopharmaceutical methods for (1) boosting p53 activity in cancer, (2) p53-dependent and p53-independent strategies for targeting p53 pathway functional restoration in p53-mutated cancer, (3) targeting p53 in immunotherapy, and (4) combination therapies targeting p53, p53 checkpoints, or mutant p53 for cancer therapy.

Keywords: P53; cancer; immunotherapy; mutant p53; targeting therapy.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Death
  • Humans
  • Mutant Proteins / metabolism
  • Mutation
  • Neoplasms* / drug therapy
  • Neoplasms* / genetics
  • Tumor Suppressor Protein p53* / genetics
  • Tumor Suppressor Protein p53* / metabolism


  • Mutant Proteins
  • Tumor Suppressor Protein p53