Targeting mutant p53 shows promise for sunscreens and skin cancer.
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.
El-Deiry
Wafik S
WS
Department of Medicine, Division of Hematology/Oncology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA. wafik@mail.med.upenn.edu
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D056741:Cyclin D; D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D045304:Cytochromes c / Q000235:genetics / Q000378:metabolism; D004781:Environmental Exposure / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D033681:Mitochondrial Membrane Transport Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D009154:Mutation / Q000187:drug effects / Q000528:radiation effects*; D009381:Neoplasms, Radiation-Induced / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D011743:Pyrimidines / Q000494:pharmacology* / Q000627:therapeutic use; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D014466:Ultraviolet Rays / Q000009:adverse effects*; D051020:bcl-X Protein / Q000235:genetics / Q000378:metabolism
C494811:BCL2L1 protein, human; C494812:Bcl2l1 protein, mouse; D056741:Cyclin D; D016213:Cyclins; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D018809:Proliferating Cell Nuclear Antigen; D011743:Pyrimidines; D016159:Tumor Suppressor Protein p53; D051020:bcl-X Protein; D045304:Cytochromes c; D011065:Poly(ADP-ribose) Polymerases; C505409:Casp3 protein, mouse; D053148:Caspase 3; C402665:CP 31398