PRIMA-1 as a cancer therapy restoring mutant p53: a review

Abstract

With a continuing increase in the prevalence of cancer, there is an increasing pressure to produce novel cancer therapies. The production of targeted cancer therapies could lead to the replacement of conventional cancer chemotherapy and, consequently, the minimization of the associated distressing side effects. This review addresses the process of restoring a mutant tumour suppressor protein, p53, in the apoptosis pathway as a potential therapeutic target for cancer therapy. Current literature highlights the small molecule PRIMA-1 as a particularly promising novel cancer therapy; however, there are currently many potential therapies being investigated; CP-31398 is another small molecule with potential anti-cancer effects. PRIMA-1 acts to restore the mutant p53 by modifying thiol groups in the core domains of the protein. Its success is well documented, with many studies in different cancer models proving its effectiveness. This, however, is not unanimous, with some questions being raised about its efficacy and other aspects such as possible resistance mechanisms as well as potentially harmful degra dation products. This said, PRIMA-1 has entered Stage II clinical trials and with more data collected on in vivo models and potential complications of the drug, it could ultimately provide an alternative to conventional cancer chemotherapy. This could therefore help to prevent cancer patients suffering the displeasing side effects with which it is associated.