Cancer Cell 15, 376–388 (2009);

Cancer Cell 15, 441–453 (2009)

Reactivating the cancer-fighting protein p53 when it has been disabled in tumour cells can rein in cancer-promoting genes and kill cancer cells in culture.

The protein is inactivated in many human cancers, allowing tumour cells to escape programmed cell death. Galina Selivanova of the Karolinska Institute in Stockholm and her co-workers report that a compound called RITA suppresses the expression of several cancer-causing genes by reactivating p53. RITA also unleashes a host of cell-death-promoting proteins, killing cancer cells.

Meanwhile, Klas Wiman, also of the Stockholm Karolinska Institute, and his colleagues show that another p53-reactivating compound, PRIMA-1, converted to reactive compounds in living cells. One of the active metabolites reacts with the sulphur-containing groups on the p53 protein, possibly restoring mutated p53 to a normal conformation. p53 is then able to trigger death in cancer cells.