Restoration of p53 to limit tumor growth

Curr Opin Oncol. 2008 Jan;20(1):90-6. doi: 10.1097/CCO.0b013e3282f31d6f.


Purpose of review: p53 mutation occurs in over half of all human tumors. Among the remaining tumors, although they may process a wild-type p53, the pathways of p53-induced cell-cycle arrest and apoptosis are deficient. Therefore, p53 serves as a unique molecular target for cancer therapy. This review focuses on the current progress regarding restoration of p53 function in human tumors for molecularly targeted therapy.

Recent findings: Targeting p53 for cancer therapy has been intensively pursued. CP-31398 was the first small molecule identified with the ability to restore the wild-type conformation to mutant p53. Subsequently, PRIMA-1 and ellipticine were found to be able to induce mutant p53-dependent cell death. Nutlin was developed to rescue wild-type p53 from degradation mediated by MDM2. More recently, p53 family members can be activated and therefore serve as substitutes of p53 in tumor cells and induce cell death.

Summary: Loss of p53 function is a characteristic of almost all human tumors. Recent advances demonstrate that reconstitution of p53 function is possible and practical as a promising antitumor strategy.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Apoptosis
  • Aza Compounds / pharmacology
  • Aza Compounds / therapeutic use
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology
  • Bridged Bicyclo Compounds, Heterocyclic / therapeutic use
  • Cell Cycle
  • Ellipticines / pharmacology
  • Ellipticines / therapeutic use
  • Genes, p53
  • Humans
  • Imidazoles / pharmacology
  • Imidazoles / therapeutic use
  • Models, Biological
  • Mutation
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism*
  • Piperazines / pharmacology
  • Piperazines / therapeutic use
  • Pyrimidines / pharmacology
  • Pyrimidines / therapeutic use
  • Tumor Suppressor Protein p53 / genetics*
  • Tumor Suppressor Protein p53 / metabolism*


  • Antineoplastic Agents
  • Aza Compounds
  • Bridged Bicyclo Compounds, Heterocyclic
  • Ellipticines
  • Imidazoles
  • Piperazines
  • Pyrimidines
  • Tumor Suppressor Protein p53
  • nutlin 1
  • ellipticine
  • 2,2-bis(hydroxymethyl)-1-azabicyclo(2,2,2,)octan-3-one
  • CP 31398