Improving pharmacological rescue of p53 function: RITA targets mutant p53

GIRARDINI J.E.; DEL SAL G.

CELL CYCLE

LANDES BIOSCIENCE

Año: 2010 vol. 9 p. 2059 - 2062

1538-4101

Despite the enormous effort put on cancer research on the last decade cancer treatment still represents a daunting challenge. A major problem in cancer therapy is the heterogeneity in human tumors that arise from the accumulation of different arrays of genetic and epigenetic alterations as well as from the diversity of heterotropic interactions that tumor cells establish with the stroma. This diversity of oncogenic mechanisms makes it difficult to identify common therapeutic strategies. However, it soon became evident that there are some similar aspects shared by the majority tumors. Inactivation of the p53 pathway is one of them, being present in most tumors. Approximately 50 % of human tumors carry mutations in the p53 gene, and in tumors without p53 mutations its tumor suppressor function is often inactivated by alterations in other components of the pathway.A breakthrough in cancer research came from the discovery of drugs able to reactivate p53’s function. The small molecule RITA recently was identified in a cell-based screening for molecules able to suppress cell proliferation in a wild-type p53-dependent manner and represents a novel and appealing possibility to improve cancer therapy. The work from Zhao et al. adds a new dimension to the potential of RITA as a chemotherapeutic drug by showing that it is able to induce an apoptotic response also in human tumor cells bearing p53 mutations.