PROGRAMMED CELL-DEATH AND RADIORESISTANCE

Whereas apoptosis is a critical mode of cell deletion in normal organi sm development, apoptotic cells are also observed in tumors. especiall y following cytotoxic treatments, leading to questions about their rol e in tumor response to therapy. We have conducted a series of studies using murine tumor models and found that the ability of the tumor cell s to undergo apoptosis correlates with tumor response to radiation. Th e best correlation was with the pretreatment apoptotic index, suggesti ng that apoptosis in some tumors may govern radiocurability by regulat ing the number of tumor clonogens. However, other roles for apoptosis in tumor response to radiation have not been ruled out. One of the imp ortant observations that has come from this work has been the heteroge neity in apoptosis propensity both within the cell population of a giv en tumor and among different types of tumors. Such findings underscore the fact that apoptosis is under complex genetic control and that som e of the same oncogenes and tumor suppressor genes that are responsibl e for tumor initiation and progression to malignancy also dictate the apoptotic response to treatment. Understanding the biochemical and mol ecular pathways that govern this process may ultimately allow the deve lopment of strategies for modulating apoptosis for therapeutic benefit .