DNA repair and resistance to chemotherapy

Abstract

DNA repair is an important mechanism of chemotherapy resistance in common human tumours. The normal tissues tolerate the drugs also, hence elucidation of normal pathways, rather than markedly resistant mutants, is more likely to be relevant. Specific repair mechanisms may deal with certain lesions (eg O6-methylguanine) but other more general mechanisms (excision repair, poly ADP ribose) can handle a wide range of lesions. The response of human cells to DNA damage is more complex than simply removing lesions. Interactions with growth factors, induction of receptors for growth factors, production of soluble mediators and secretion of plasminogen activator are parts of a cellular and tissue response. These processes may be more active in earlier, less differentiated cells which are more resistant to radiotherapy and chemotherapy. The genetic instability of cancer cells may be related to inappropriately activated DNA repair pathways.