The role of radiation-induced apoptosis as a determinant of tumor responses to radiation therapy

Ionizing radiation is an effective means of killing tumor cells. Approximat ely 50% of all American cancer patients are treated with radiotherapy at so me time during the course of their disease, making radiation one of the mos t widely used cytotoxic therapies. Currently, much effort is focused on und erstanding the molecular pathways that regulate tumor cell survival followi ng radiotherapy, with the long term goal of developing novel therapeutic st rategies for specifically sensitizing tumors to radiation. At present, ther e is particular interest in the role of tumor cell apoptotic potential as a regulator of both intrinsic and extrinsic determinants of the response of tumors to radiation therapy. Here we review what is currently known about t he role of apoptosis as a mechanism of tumor cell killing by ionizing radia tion and the relative contribution of apoptosis to cellular radiosensitivit y and the ability to control human cancers using radiotherapy. The followin g topics will be discussed: (1) radiation-induced apoptosis in normal and m alignant cells, (2) clinical findings with respect to apoptosis in human ca ncers treated with radiotherapy, (3) the contribution of apoptosis to intri nsic radiosensitivity in vitro, (4) the relevance of apoptosis to treatment outcome in experimental tumor models in vivo and (5) the potential of expl oiting apoptosis as a means to improve the therapeutic efficacy of radiothe rapy.