Radiosensitivity of tumor cells. Oncogenes and apoptosis.
The success of treatment of cancer patients by radiotherapy largely depends on tumor radiosensitivity. Several molecular factors that determine the sensitivity of tumor cells to ionizing radiation have been identified during the last couple of years. Some of these factors are known as oncogenes and tumor suppressor genes. This review focuses on the influence of some of these molecular factors on a major determinant of radiosensitivity: i.e. programmed cell death or apoptosis. The crucial molecular step in ionizing radiation-induced apoptosis is the release of mitochondrial cytochrome c into the cell's cytosol. The ways the tumor suppressor protein p53, as well as the oncogenes ras and raf, c-myc and Bcl-2 can influence this process at different stages are presented. As will be discussed, the result of activation of an oncoprotein on tumor radiosensitivity depends on its mechanism of action and on the presence of other (oncogenic) factors, since complex interactions among many molecular factors determine the delicate balance between cell proliferation and cell death. The ongoing identification and characterization of factors influencing apoptosis will eventually make it possible to predict tumor radiosensitivity and thereby improve cancer treatment.
Peltenburg
L T
LT
Department of Clinical Oncology, Leiden University Medical Center, The Netherlands. peltenburg@lumc.nl
D017209:Apoptosis / Q000235:genetics / Q000528:radiation effects*; D016147:Genes, Tumor Suppressor / Q000502:physiology; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy*; D011519:Proto-Oncogenes / Q000502:physiology*; D011836:Radiation Tolerance / Q000235:genetics*