p53 as a drug target in cancer therapy

The tumour suppressor gene p53 is mutated in various human cancers. The loss of p53 function predisposes to cancer and it has been suggested that the efficacy of chemotherapy and radiotherapy depends on the presence of a functional p53. The central role of p53 in cancer has stimulated intense research activity and various strategies to identify new anticancer compounds that modulate the p53 pathway are currently under investigation. These approaches rely on very different principles. Some involve replacement gene therapy where p53 is reintroduced into tumour cells or engineered viruses that selectively eliminate cells with an altered p53 pathway. Others are based on the synthesis of new molecules that stabilise the structure of the mutant proteins or that activate either wild type or mutant proteins. Finally, others use antibodies that specifically interact with tumour cells. In this review, recent patent applications and the progress currently being made on these different approaches are analysed.