A Distinctive Multiple Drug Resistance Phenotype Expressed by Tumor Cells Following Exposure to X-Irradiation

Abstract

Resistance to drug therapy is considered one of the main reasons for treatment failures. Laboratory-based mechanistic studies aim to elucidate the biochemical/biological bases for resistance to the varied classes of antitumor drugs in current clinical usage, so as to design rationale ways of either overcoming or circumventing any expression of drug resistance, preventing its development or interfering with the mechanisms themselves. Clinical resistance to chemotherapy is encountered not only following treatment with single agents or after multiple drugs, but also has been identified in subgroups of patients with solid tumors who have received prior radiotherapy (cf. review by Hill, 1991). Indeed, our early investigative studies of the treatment of head and neck cancer highlighted the fact that patients whose tumors had been irradiated not only had reduced response rates to subsequent combination chemotherapy, but also had significantly reduced survival figures (Hill et al., 1984). In view of the major role of radiotherapy in cancer management we considered it importance to determine the molecular basis for this expression of drug resistance by tumor cells following their exposure to X-irradiation and in particular to establish whether any novel or distinctive mechanisms operated, different from those more generally studied and known to result from drug selection or exposure.