TY - JOUR
T1 - Chemical modifiers of cancer treatment
AU - Coleman, C. N.
AU - Bump, E. A.
AU - Kramer, R. A.
N1 - Funding Information:
The theory and mechanism of action of electron-affinic sensitizers, sulfhydryls as protectors, and oxygen were discussed in a number of papers. In his introductory key-note lecture, Dr. Palcic outlined the argument for differing types of lesions after irradiation in nitrogen and in air with a greater preponderance of alpha-type damage and less repair of damage occurring under hypoxic conditions. Poster papers presented information on the existence of the action of sulfhydryl protectors as solvent or solute scavengers and reactors with target radicals. Another poster actually proposed two possible target radicals, a Supported by the National Institutes of Health, National Cancer Institute Grants Number CA 2 I744 and CA 2 1439.
PY - 1988
Y1 - 1988
N2 - Chemical modification is a concept in cancer therapy in which the state of tumor cells or normal tissues is modified such that a therapeutic gain can be achieved using conventional therapeutic modalities. Hypoxic zones targeted as cells within them may be radiation resistant, poorly perfused by chemotherapeutic agents, and possibly drug resistant due to hypoxia-related gene amplification. Nitroimidazoles have gained particular attention as chemical modifiers because they can increase the radiation sensitivity of hypoxic cells, are cytotoxic to hypoxic cells, can increase sensitivity to chemotherapeutic agents, and are useful for imaging hypoxic cells. While both radiosensitization and chemosensitization require hypoxia, the mechanism of the enhancement of each of the modalities is different. The 2-nitroimidazole hypoxic sensitizers SR 2508 and Ro-03-8799, which are less toxic than the prototype misonidazole (Miso), are in clinical trials, and dual function molecules that include a hypoxic sensitizer and alkylating function are being developed. The presence of both acutely and chronically hypoxic cells in animal tumors has been demonstrated by new imaging techniques. Oxygen delivery to tumors is being altered by the use of perfluorocarbons, and agents that alter hemoglobin affinity for oxygen. Compounds that are selectively toxic to hypoxic cells are being developed. Nonhypoxic modifiers are also being investigated. Thiol modification, particularly the alteration of glutathione concentration, has complex effects on the cell's biochemistry, in addition to affecting the competition between oxygen and thiol groups for the restoration and fixation of radiation-induced radicals. WR-2721 is being studied as a means of reducing the normal tissue toxicity of radiation and chemotherapy. Increased thiol concentration may be a mechanism of cross-resistance between certain chemotherapeutic agents and radiation.
AB - Chemical modification is a concept in cancer therapy in which the state of tumor cells or normal tissues is modified such that a therapeutic gain can be achieved using conventional therapeutic modalities. Hypoxic zones targeted as cells within them may be radiation resistant, poorly perfused by chemotherapeutic agents, and possibly drug resistant due to hypoxia-related gene amplification. Nitroimidazoles have gained particular attention as chemical modifiers because they can increase the radiation sensitivity of hypoxic cells, are cytotoxic to hypoxic cells, can increase sensitivity to chemotherapeutic agents, and are useful for imaging hypoxic cells. While both radiosensitization and chemosensitization require hypoxia, the mechanism of the enhancement of each of the modalities is different. The 2-nitroimidazole hypoxic sensitizers SR 2508 and Ro-03-8799, which are less toxic than the prototype misonidazole (Miso), are in clinical trials, and dual function molecules that include a hypoxic sensitizer and alkylating function are being developed. The presence of both acutely and chronically hypoxic cells in animal tumors has been demonstrated by new imaging techniques. Oxygen delivery to tumors is being altered by the use of perfluorocarbons, and agents that alter hemoglobin affinity for oxygen. Compounds that are selectively toxic to hypoxic cells are being developed. Nonhypoxic modifiers are also being investigated. Thiol modification, particularly the alteration of glutathione concentration, has complex effects on the cell's biochemistry, in addition to affecting the competition between oxygen and thiol groups for the restoration and fixation of radiation-induced radicals. WR-2721 is being studied as a means of reducing the normal tissue toxicity of radiation and chemotherapy. Increased thiol concentration may be a mechanism of cross-resistance between certain chemotherapeutic agents and radiation.
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U2 - 10.1200/JCO.1988.6.4.709
DO - 10.1200/JCO.1988.6.4.709
M3 - Review article
C2 - 3282035
AN - SCOPUS:0023892054
SN - 0732-183X
VL - 6
SP - 709
EP - 733
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 4
ER -