POTENTIAL MOLECULAR TARGETS FOR MANIPULATING THE RADIATION RESPONSE

Citation
A. Maity et al., POTENTIAL MOLECULAR TARGETS FOR MANIPULATING THE RADIATION RESPONSE, International journal of radiation oncology, biology, physics, 37(3), 1997, pp. 639-653
Citations number
180
Language
INGLESE
art.tipo
Review
Categorie Soggetti
Oncology,"Radiology,Nuclear Medicine & Medical Imaging
ISSN journal
0360-3016
Volume
37
Issue
3
Year of publication
1997
Pages
639 - 653
Database
ISI
SICI code
0360-3016(1997)37:3<639:PMTFMT>2.0.ZU;2-R
Abstract
Recent advances in our understanding of the molecular events that occu r following ionizing radiation leading to DNA damage and repair, apopt osis, and cell-cycle arrests suggest new ways in which the radiation r esponse might be manipulated. Specific targets which, if inactivated, might increase radiosensitivity include Ras, which has been implicated in the radioresistant phenotype, and components of DNA-dependent prot ein kinase or other molecules involved in the recognition or repair of DNA damage. In some tumors, apoptosis is an important mode of cell de ath following radiation, so agents that promote this may prove useful therapeutically. Conversely, side effects may result from radiation-in duced apoptosis of normal tissues: for example, pneumonitis following the destruction of endothelial cells in the pulmonary vasculature. The refore, decreasing apoptosis in these tissues may reduce late effects. It may also be possible to prevent late effects such as fibrosis by b locking the induction of certain genes such as transforming growth fac tor beta. Cell-cycle regulation is another area that could be manipula ted to increase radiosensitivity. There is evidence that the G2 delay following radiation is important in protecting cells from death. Aboli tion of this delay may increase radiosensitivity, especially in cells with mutant p53 that have lost the G1 checkpoint. (C) 1997 Elsevier Sc ience Inc.