P53, Apoptosis, and Chemosensitivity

Abstract

Basic cancer research provides a theoretical foundation for rational approaches to improve cancer diagnosis, prognosis, and therapy. For example, the p53 tumor suppressor can facilitate apoptosis induced by anticancer agents, implying that p53 mutations should contribute to radiation and drug resistance in human tumors. Indeed, p53 mutations do correlate with drug resistance in some tumor types, and reintroduction of p53 into p53 mutant tumors enhances chemosensitivity in vitro and in vivo. However, in many settings, the relationship between p53, apoptosis, and chemosensitivity remains ambiguous. Although methodological shortcomings clearly contribute to this confusion, the situation is further confounded by the fact that p53’s apoptotic activity depends on context. Hence, the chemotherapeutic agent, tumor type, and genetic background may each impact on the relationship between p53 and chemosensitivity. An improved understanding of this complexity will be necessary to guide future efforts in exploiting p53 or other cancer genes for improved cancer treatment.