PMID- 9516945
OWN - NLM
STAT- MEDLINE
DCOM- 19980409
LR  - 20220330
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 4
IP  - 1
DP  - 1998 Jan
TI  - The role of DNA mismatch repair in drug resistance.
PG  - 1-6
AB  - Loss of DNA mismatch repair (MMR) has been observed in a variety of human 
      cancers. In addition to predisposing to oncogenesis, loss of MMR activity is of 
      concern with respect to the use of chemotherapeutic agents to treat established 
      tumors. Loss of MMR results in drug resistance directly by impairing the ability 
      of the cell to detect DNA damage and activate apoptosis and indirectly by 
      increasing the mutation rate throughout the genome. The MMR proteins are involved 
      in mediating the activation of cell cycle checkpoints and apoptosis in response 
      to DNA damage. MMR-deficient cells have been reported to be resistant to the 
      methylating agents procarbazine and temozolomide, the alkylating agent busulfan, 
      the platinum-containing drugs cisplatin and carboplatin, the antimetabolite 
      6-thioguanine, and the topoisomerase II inhibitors etoposide and doxorubicin. In 
      the case of cisplatin, busulfan, temozolomide, and procarbazine, the degree of 
      resistance has been shown to be sufficient to produce a large difference in 
      clinical responsiveness in vivo in tumor model systems. The available preclinical 
      data suggest that tumors that contain a significant fraction of cells deficient 
      in MMR will demonstrate reduced responsiveness to specific drugs. The challenge 
      now is to assess the clinical significance of the presence of deficient cells in 
      tumors and to discover drugs that retain activity against MMR-deficient cells.
FAU - Fink, D
AU  - Fink D
AD  - Department of Medicine, University of California at San Diego, La Jolla 
      92093-0058, USA.
FAU - Aebi, S
AU  - Aebi S
FAU - Howell, S B
AU  - Howell SB
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (Alkylating Agents)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Organoplatinum Compounds)
RN  - FTK8U1GZNX (Thioguanine)
SB  - IM
MH  - Alkylating Agents/pharmacology
MH  - Animals
MH  - Antineoplastic Agents/*pharmacology
MH  - Cell Cycle
MH  - *DNA Repair
MH  - *Drug Resistance, Neoplasm
MH  - Humans
MH  - Organoplatinum Compounds/pharmacology
MH  - Thioguanine/pharmacology
RF  - 75
EDAT- 1998/05/14 00:00
MHDA- 1998/05/14 00:01
CRDT- 1998/05/14 00:00
PHST- 1998/05/14 00:00 [pubmed]
PHST- 1998/05/14 00:01 [medline]
PHST- 1998/05/14 00:00 [entrez]
PST - ppublish
SO  - Clin Cancer Res. 1998 Jan;4(1):1-6.