In search of p53 target genes for the therapeutic manipulation of cancer.
As a tumor suppressor protein, p53 plays a crucial role in cancer development. Direct associations between p53, apoptosis and drug response suggest that targeting genes/gene products downstream of p53 may have clinical benefits. The completion of the human genome project and the availability of microarray technology have led to new ways in which to define the global regulatory network of p53 and to search for oncogenes in the p53 pathway. A crucial step toward antitumor drug discovery is the mapping of p53 transcriptomes onto cancer phenomes. In this review, recent developments in the genome-wide search of p53 target genes are discussed, along with current efforts in high-throughput antitumor target discovery in the p53 pathway and recent progress in the pharmacological modulation of targets downstream of p53 for effective cancer therapy.
Liu
Suxing
S
Biological Research-Oncology, Schering-Plough Research Institute, Kenilworth, NJ 07033, USA. suxing.liu@spcorp.com
Seidel-Dugan
Cynthia
C
D000818:Animals; D015195:Drug Design; D018390:Gene Targeting; D016158:Genes, p53 / Q000187:drug effects*; D015316:Genetic Therapy; D006801:Humans; D009369:Neoplasms / Q000628:therapy*