RESISTANCE MECHANISMS AND THEIR REGULATION IN LUNG-CANCER

Data obtained from multiple sources indicate that no single mechanism can explain the drug resistance and the poor prognosis of patients wit h lung cancer. The resistance-related proteins P-glycoprotein, glutath ione-dependent enzymes, topoisomerase II, metallothioneins, O-6-alkylg uanine-DNA alkyltransferase, thymidylate synthase, dihydrofolate reduc tase and heat shock proteins have been found in lung carcinomas, but t hese alone cannot explain the drug-resistant phenotype. Cell cycle-rel ated proteins, angiogenic factors, protooncogenes, and tumor suppresso r genes also play a role in the phenotype that is resistant lung cance r. A key future challenge involves determining the relative quantitati ve contributions of each of these mechanisms to overall resistance.