Sister chromatid exchange assay as a predictor of tumor chemoresponse.
Sister Chromatid Exchanges (SCEs) are known to enhance as a consequence of exposure to various mutagenic agents and appear to indicate DNA damaging effects and/or subsequent repair by homologous recombination (HR). DNA damage plays an interesting role in the majority of mechanisms underlying the effects of antitumor drugs, since the genetic activity of the plethora of these agents is due to their ability to damage the DNA. The DNA-effects of antitumor agents towards normal cells (genotoxicity) are great drawbacks of antitumor therapy and are connected to important adverse health effects in cancer patients undergoing chemotherapy. On the other hand, failure of chemotherapy in many cases is due to the DNA repair ability which cancer, like normal cells, also possess. As both DNA repair and genotoxic exposure are expected to vary among patients, correlating SCEs frequencies with only individual repair capacity may be feasible to predict. Cancer risk has not been observed to be associated with high SCEs levels. Since the administration of effective antitumor drugs with limited adverse effects is of great importance in the success of anticancer therapy, a lot of interest has been directed toward the development of methods and approaches that would enable the correct selection of appropriate drugs prior to the initiation of therapy on an individual basis. To this effect, more than 30 years ago, an investigation of the ability of the in vitro and the in vivo SCEs-assay to predict the in vitro and in vivo sensitivity of tumor cells to newly synthesized drugs or to those already in use began. In this short review a critical appraisal of the SCEs-assay as an important biomarker used for predicting cancer chemo-response as well as a summary of the key findings from several studies published within the last 20 years in this field is performed.
Dept. of Med. Biology and Genetics, Med. Faculty, Aristotle University of Thessaloniki, 54124, Greece. Electronic address: dmourela@auth.gr.
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Mourelatos
D000970:Antineoplastic Agents / Q000627:therapeutic use; D004249:DNA Damage / Q000235:genetics; D004260:DNA Repair / Q000187:drug effects / Q000235:genetics; D006801:Humans; D009369:Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics*; D011237:Predictive Value of Tests; D012854:Sister Chromatid Exchange / Q000235:genetics*
D000970:Antineoplastic Agents
Predictor; SCE-assay; Tumor chemoresponse