Disarming mutant p53 oncogenic function.
In the last decade intensive research has confirmed the long standing hypothesis that some p53 point mutants acquire novel activities able to cooperate with oncogenic mechanisms. Particular attention has attracted the ability of several such mutants to actively promote the development of aggressive and metastatic tumors in vivo. This knowledge opens a new dimension on rational therapy design, suggesting novel strategies based on pharmacological manipulation of those neomorphic activities. P53 point mutants have several characteristics that make them attractive targets for anti-cancer therapies. Remarkably, mutant p53 has been found predominantly in tumor cells and may act pleiotropically by interfering with a variety of cellular processes. Therefore, drugs targeting mutant p53 may selectively affect tumor cells, inactivating simultaneously several mechanisms of tumor promotion. Moreover, the high frequency of missense mutations on the p53 gene suggests that interfering with mutant p53 function may provide a valuable approach for the development of efficient therapies able to target a wide range of tumor types.
Institute of Molecular and Cell Biology of Rosario, IBR-CONICET, Argentina.
Javier E
JE
Girardini
Laboratorio Nazionale CIB (LNCIB), Area Science Park, Trieste, Italy; Dipartimento di Scienze della Vita, Università degli Studi di Trieste, 34127 Trieste, Italy.
Carolina
C
Marotta
Laboratorio Nazionale CIB (LNCIB), Area Science Park, Trieste, Italy; Dipartimento di Scienze della Vita, Università degli Studi di Trieste, 34127 Trieste, Italy. Electronic address: delsal@lncib.it.
Giannino
G
Del Sal
D000818:Animals; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
D016159:Tumor Suppressor Protein p53
Cancer; Mutant p53; Therapeutic strategies