TY - JOUR
T1 - Molecular mechanisms of resistance and toxicity associated with platinating agents
AU - Rabik, Cara A.
AU - Dolan, M. Eileen
N1 - Funding Information:
Some of the work in this review was supported by NIH/NCI grant CA81485 and Medical Scientist National Research Service Award Grant 5 T32 GM07281 (C.A.R.).
PY - 2007/2
Y1 - 2007/2
N2 - Platinating agents, including cisplatin, carboplatin, and oxaliplatin, have been used clinically for nearly 30 years as part of the treatment of many types of cancers, including head and neck, testicular, ovarian, cervical, lung, colorectal and relapsed lymphoma. The cytotoxic lesion of platinating agents is thought to be the platinum intrastrand crosslink that forms on DNA, although treatment activates a number of signal transduction pathways. Treatment with these agents is characterized by resistance, both acquired and intrinsic. This resistance can be caused by a number of cellular adaptations, including reduced uptake, inactivation by glutathione and other anti-oxidants, and increased levels of DNA repair or DNA tolerance. Here we investigate the pathways that treatment with platinating agents activate, the mechanisms of resistance, potential candidate genes involved in the development of resistance, and associated clinical toxicities. Although the purpose of this review is to provide an overview of cisplatin, carboplatin, and oxaliplatin, we have focused primarily on preclinical data that has clinical relevance generated over the past five years.
AB - Platinating agents, including cisplatin, carboplatin, and oxaliplatin, have been used clinically for nearly 30 years as part of the treatment of many types of cancers, including head and neck, testicular, ovarian, cervical, lung, colorectal and relapsed lymphoma. The cytotoxic lesion of platinating agents is thought to be the platinum intrastrand crosslink that forms on DNA, although treatment activates a number of signal transduction pathways. Treatment with these agents is characterized by resistance, both acquired and intrinsic. This resistance can be caused by a number of cellular adaptations, including reduced uptake, inactivation by glutathione and other anti-oxidants, and increased levels of DNA repair or DNA tolerance. Here we investigate the pathways that treatment with platinating agents activate, the mechanisms of resistance, potential candidate genes involved in the development of resistance, and associated clinical toxicities. Although the purpose of this review is to provide an overview of cisplatin, carboplatin, and oxaliplatin, we have focused primarily on preclinical data that has clinical relevance generated over the past five years.
KW - Cisplatin
KW - DNA damage
KW - Drug resistance
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U2 - 10.1016/j.ctrv.2006.09.006
DO - 10.1016/j.ctrv.2006.09.006
M3 - Review article
C2 - 17084534
AN - SCOPUS:33846404174
SN - 0305-7372
VL - 33
SP - 9
EP - 23
JO - Cancer Treatment Reviews
JF - Cancer Treatment Reviews
IS - 1
ER -