Targeting mutant p53 shows promise for sunscreens and skin cancer

J Clin Invest. 2007 Dec;117(12):3658-60. doi: 10.1172/JCI34251.

Abstract

Chronic exposure to UV light is a risk factor for skin cancer in which signature mutations in the p53 tumor suppressor gene occur due to DNA damage and contribute to cancer development. In this issue of the JCI, Tang et al. report on their study of a nonimmunodeficient mouse model of UVB-induced skin cancer and human skin carcinoma cells and show that the mutant p53 conformation-modifying drug CP-31398 not only treats these tumors but also prevents them (see the related article beginning on page 3753). These studies have important implications for chemoprevention as well as therapy of common, mutant p53-driven tumors.

Publication types

  • Comment

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Apoptosis / radiation effects
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Cell Line, Tumor
  • Cell Transformation, Neoplastic / drug effects*
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • Cell Transformation, Neoplastic / pathology
  • Cell Transformation, Neoplastic / radiation effects
  • Cyclin D
  • Cyclins / genetics
  • Cyclins / metabolism
  • Cytochromes c / genetics
  • Cytochromes c / metabolism
  • Environmental Exposure / adverse effects*
  • Female
  • Humans
  • Male
  • Mice
  • Mice, Hairless
  • Mitochondria / genetics
  • Mitochondria / metabolism
  • Mitochondria / pathology
  • Mitochondrial Membrane Transport Proteins / antagonists & inhibitors
  • Mitochondrial Membrane Transport Proteins / genetics
  • Mitochondrial Membrane Transport Proteins / metabolism
  • Mitochondrial Permeability Transition Pore
  • Mutation / drug effects
  • Mutation / radiation effects*
  • Neoplasms, Radiation-Induced / drug therapy*
  • Neoplasms, Radiation-Induced / genetics
  • Neoplasms, Radiation-Induced / metabolism
  • Neoplasms, Radiation-Induced / pathology
  • Poly(ADP-ribose) Polymerases / genetics
  • Poly(ADP-ribose) Polymerases / metabolism
  • Proliferating Cell Nuclear Antigen / genetics
  • Proliferating Cell Nuclear Antigen / metabolism
  • Protein Transport / drug effects
  • Protein Transport / genetics
  • Protein Transport / radiation effects
  • Pyrimidines / pharmacology*
  • Pyrimidines / therapeutic use
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / genetics
  • Skin Neoplasms / metabolism
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*
  • Ultraviolet Rays / adverse effects*
  • bcl-X Protein / genetics
  • bcl-X Protein / metabolism

Substances

  • BCL2L1 protein, human
  • Bcl2l1 protein, mouse
  • Cyclin D
  • Cyclins
  • Mitochondrial Membrane Transport Proteins
  • Mitochondrial Permeability Transition Pore
  • Proliferating Cell Nuclear Antigen
  • Pyrimidines
  • Tumor Suppressor Protein p53
  • bcl-X Protein
  • Cytochromes c
  • Poly(ADP-ribose) Polymerases
  • Casp3 protein, mouse
  • Caspase 3
  • CP 31398