Antineoplastic drug resistance and DNA repair.
Important aspects of the DNA repair mechanisms in mammalian, and especially human, cells are reviewed. The DNA repair processes are essential in the maintenance of the integrity of the DNA and in the defense against cancer. It has recently been discovered that the DNA repair efficiency differs in different regions of the genome and that active genes are preferentially repaired. There is mounting evidence that DNA repair processes play a role in the development of drug resistance by tumor cells. We will discuss such data as well as further approaches to clarify the relationship between DNA repair and antineoplastic drug resistance. Specifically, there is an increasing need to investigate the intragenomic heterogeneity of DNA repair and correlate the repair efficiency in specific genes to aspects of drug resistance. We also discuss the therapeutic potential of inhibiting the DNA repair processes and thereby possibly overcoming drug resistance.
Burt
R K
RK
Clinical Oncology Program, National Cancer Institute, National Institutes of Health, Bethesda, MD.
Poirier
M C
MC
Link
C J
CJ
Bohr
V A
VA
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D004260:DNA Repair / Q000187:drug effects*; D004273:DNA, Neoplasm / Q000187:drug effects* / Q000235:genetics; D004259:DNA-Directed DNA Polymerase / Q000235:genetics; D004351:Drug Resistance / Q000235:genetics*; D005809:Genes, Regulator / Q000235:genetics*; D006801:Humans; D066298:In Vitro Techniques; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D011740:Pyrimidine Dimers / Q000235:genetics
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D011740:Pyrimidine Dimers; D004259:DNA-Directed DNA Polymerase