Role of mismatch repair and MGMT in response to anticancer therapies

被引：48
作者：
Casorelli, Ida [1 ]
Russo, Maria Teresa [1 ]
Bignami, Margherita [1 ]
机构：
[1] Ist Super Sanita, Dept Environm & Primary Prevent, Sect Expt Carcinogenesis, I-00161 Rome, Italy
来源：
ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY | 2008年 / 8卷 / 04期
关键词：
D O I：
10.2174/187152008784220276
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Tumor resistance to cytotoxic chemotherapy drugs and their toxicity to normal cells are major clinical obstacles to anticancer therapy effectiveness. Alterations in various DNA repair pathways play a key role in the development of both mechanisms of drug resistance and toxicity. Since deregulation of the DNA damage response and alterations in DNA repair pathways are relatively common in human cancer, the knowledge of these alterations in cancer cells would be an important predictive factor for the clinical response to chemotherapy and a useful guide in designing an appropriate therapeutic strategy. This review is focused on the mismatch repair ( MMR) pathway and the O-6-methylguanine-DNA-methyltransferase ( MGMT) repair protein. In particular, we examine how inactivation of these DNA repair mechanisms might affect the response of tumor cells to chemotherapy, with a special emphasis on agents inducing methylation and oxidative DNA damage and interstrand DNA cross-links ( ICLs). In addition, we provide novel experimental evidence indicating that MMR is required for efficient repair of ICLs via stabilization of RAD51 containing repair intermediates. Finally, we discuss possible emerging therapeutical strategies for treating MMR-defective tumors.
引用
收藏
页码：368 / 380
页数：13
相关论文
共 114 条
[11]   Unmasking a killer:: DNA O6-methylguanine and the cytotoxicity of methylating agents [J].
Bignami, M ;
O'Driscoll, M ;
Aquilina, G ;
Karran, P .
MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH, 2000, 462 (2-3) :71-82
[12]   Mismatch repair and response to DNA-damaging antitumour therapies [J].
Bignami, M ;
Casorelli, I ;
Karran, P .
EUROPEAN JOURNAL OF CANCER, 2003, 39 (15) :2142-2149
[13]   DEFECTIVE MISMATCH BINDING AND A MUTATOR PHENOTYPE IN CELLS TOLERANT TO DNA DAMAGE [J].
BRANCH, P ;
AQUILINA, G ;
BIGNAMI, M ;
KARRAN, P .
NATURE, 1993, 362 (6421) :652-654
[14]   Spontaneous development of drug resistance: mismatch repair and p53 defects in resistance to cisplatin in human tumor cells [J].
Branch, P ;
Masson, M ;
Aquilina, G ;
Bignami, M ;
Karran, P .
ONCOGENE, 2000, 19 (28) :3138-3145
[15]   Microsatellite instability in colorectal cancer is associated with local lymphocyte infiltration and low frequency of distant metastases [J].
Buckowitz, A ;
Knaebel, HP ;
Benner, A ;
Bläker, H ;
Gebert, J ;
Kienle, P ;
Doeberitz, MV ;
Kloor, M .
BRITISH JOURNAL OF CANCER, 2005, 92 (09) :1746-1753
[16]   Phenotypic heterogeneity in nucleotide excision repair mutants of rodent complementation groups 1 and 4 [J].
Busch, DB ;
vanVuuren, H ;
deWit, J ;
Collins, A ;
Zdzienicka, MZ ;
Mitchell, DL ;
Brookman, KW ;
Stefanini, M ;
Riboni, R ;
Thompson, LH ;
Albert, RB ;
vanGool, AJ ;
Hoeijmakers, J .
MUTATION RESEARCH-DNA REPAIR, 1997, 383 (02) :91-106
[17]   Total loss of MHC class I in colorectal tumors can be explained by two molecular pathways:: β2-microglobulin inactivation in MSI-positive tumors and LMP7/TAP2 downregulation in MSI-negative tumors [J].
Cabrera, CM ;
Jiménez, P ;
Cabrera, T ;
Esparza, C ;
Ruiz-Cabello, F ;
Garrido, F .
TISSUE ANTIGENS, 2003, 61 (03) :211-219
[18]  
Caporali S, 2004, MOL PHARMACOL, V66, P478
[19]  
CASORELLI I, 2003, DNA REPAIR, V142, P1
[20]   Processing of O-6-methylguanine by mismatch correction in human cell extracts [J].
Ceccotti, S ;
Aquilina, G ;
Macpherson, P ;
Yamada, M ;
Karran, P ;
Bignami, M .
CURRENT BIOLOGY, 1996, 6 (11) :1528-1531
12345678910