The promise and obstacle of p53 as a cancer therapeutic agent

A. C. Willis, Xinbin Chen

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

p53 is a tumor suppressor gene that is mutated in greater than 50% of human cancers. The action of p53 as a tumor suppressor involves inhibition of cell proliferation through cell cycle arrest and/or apoptosis. Loss of p53 function therefore allows the uncontrolled proliferation associated with cancerous cells. While design of most anti-cancer agents has focused on targeting and inactivating cancer promoting targets, such as oncogenes, recent attention has been given to restoring the lost activity of tumor suppressor genes. Because the loss of p53 function is so prevalent in human cancer, this protein is an ideal candidate for such therapy. Several gene therapeutic strategies have been employed in the attempt to restore p53 function to cancerous cells. These approaches include introduction of wild-type p53 into cells with mutant p53; the use of small molecules to stabilize mutant p53 in a wild-type, active conformation; and the introduction of agents to prevent degradation of p53 by proteins that normally target it. In addition, because mutant p53 has oncogenic gain of function activity, several approaches have been investigated to selectively target and kill cells harboring mutant p53. These include the introduction of mutant viruses that cause cell death only in cells with mutant p53 and the introduction of a gene that, in the absence of functional p53, produces a toxic product. Many obstacles remain to optimize these strategies for use in humans, but, despite these, restoration of p53 function is a promising anti-cancer therapeutic approach.

Original languageEnglish (US)
Pages (from-to)329-345
Number of pages17
JournalCurrent Molecular Medicine
Volume2
Issue number4
DOIs
StatePublished - Jun 2002
Externally publishedYes

Fingerprint

Genes
Tumors
Neoplasms
Tumor Suppressor Genes
Therapeutics
Poisons
Cell proliferation
Cell death
Viruses
Restoration
Conformations
Cell Cycle Checkpoints
Oncogenes
Proteins
Proteolysis
Cells
Cause of Death
Apoptosis
Cell Death
Degradation

Keywords

  • Cancer therapy
  • Gene therapy
  • p53

ASJC Scopus subject areas

  • Biochemistry

Cite this

The promise and obstacle of p53 as a cancer therapeutic agent. / Willis, A. C.; Chen, Xinbin.

In: Current Molecular Medicine, Vol. 2, No. 4, 06.2002, p. 329-345.

Research output: Contribution to journalArticle

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