The p53 guardian of the genome is inactivated in the majority of cancers, mostly 
through missense mutations that cause single residue changes in the DNA binding 
core domain of the protein. Not only do such mutations result in the abrogation 
of wild-type p53 activity, but the expressed p53 mutant proteins also tend to 
gain oncogenic functions, such as interference with wild-type p53-independent 
apoptosis. Because p53 mutants are highly expressed in cancer cells and not in 
normal cells, their reactivation to wild-type p53 function may eliminate the 
cancer by apoptosis or another p53-dependent mechanism. Several studies that 
embarked on this quest for reactivation have succeeded in restoring wildtype p53 
activity to several p53 mutants. However, mutants with more extensive structural 
changes in the DNA binding core domain may be refractory to reactivation to the 
wild-type p53 phenotype. Therefore, understanding the structure and functions of 
oncogenic p53 mutants may lead to more potent reactivation modalities or to the 
ability to eliminate mutant p53 gain of function.