p53 gene in treatment of hepatic carcinoma: Status quo

Table 1 Abnormal p53 status detected in HCC with probable mechanisms

Endogenous status of p53 or its pathways	Probable mechanisms
Mutation of p53 gene	Point mutation, allele deletion, insertion, etc.
Loss of or decrease in wt-p53 expression	Enhanced p53 degradation, complex formation
Hyperactivities of negative regulators of p53	No p53 mutation, over- expressed negative regulators of p53 attenuate its function
Increased diversity of p53 aberration	Progression of HCC
Presence of serum anti-p53 antibodies	Over-expression of wt-p53, presence of mt-p53, or both

Table 2 Approaches for restoring tumor suppression function of p53 in the treatment of HCC

Strategies	Therapeutic effects
Chemotherapy or radiotherapy	Inducing p53-dependent apoptosis in tumor cells with wt-p53
Supplying exogenous wt-p53 by gene delivery	Suppressing growth of both mutant and wild-type p53-containing tumor cells
Overexpression of ARF	Blocking p53 degradation pathways to induce p53 triggered tumor cell death
Interruption of MDM2-p53 interaction	Preventing MDM2-mediated p53 ubiquitinationand degradation to restore transactivation
Molecules stabilizing the active conformation of the protein	Rescuing mt-p53 to restore p53 function

Table 3 Comparison of several characteristics of rAd-p53 with oncolytic virus products

Products	Characteristics
rAd-p53	p53 gene is transfected into HCC cells with recombinant adenoviral vector expressing wt-p53
Advexin	Larger host range, low pathogenicity to human, replication-impaired adenoviral vector carrying the p53 gene
Gendicine	The first commercial gene therapy product in the world approved by SFDA
SCH58500	Replication-deficient type 5 adenovirus vector expressing human wt-p53 under control of cytomegalovirus promoter
Oncolytic viruses	Incapable of replicating in normal cells but selectively replicating in p53-defective tumor cells to lyse them
ONYX-015	Tumor-selective replicating virus, the prototype for oncolytic adenoviral therapy
CNHK300-mE	Replication-competent with advantages of both gene and virus therapies