title: Resistance mechanisms and their regulation in lung cancer.
abstract: Data obtained from multiple sources indicate that no single mechanism can explain the drug resistance and the poor prognosis of patients with lung cancer. The resistance-related proteins P-glycoprotein, glutathione-dependent enzymes, topoisomerase II, metallothioneins, O-6-alkylguanine-DNA alkyltransferase, thymidylate synthase, dihydrofolate reductase and heat shock proteins have been found in lung carcinomas, but these alone cannot explain the drug-resistant phenotype. Cell cycle-related proteins, angiogenic factors, protooncogenes, and tumor suppressor genes also play a role in the phenotype that is resistant lung cancer. A key future challenge involves determining the relative quantitative contributions of each of these mechanisms to overall resistance.
authors.affiliation: Department of Oncological Diagnostics and Therapy, German Cancer Research Center, Heidelberg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Volm
authors.forename: J
authors.initials: J
authors.lastname: Mattern
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000187:drug effects / Q000502:physiology; D000818:Animals; D004250:DNA Topoisomerases, Type II / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D016147:Genes, Tumor Suppressor; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D008668:Metallothionein / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D011519:Proto-Oncogenes; D013762:Tetrahydrofolate Dehydrogenase / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D013940:Thymidylate Synthase / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D006360:Heat-Shock Proteins; D008668:Metallothionein; D013762:Tetrahydrofolate Dehydrogenase; D013940:Thymidylate Synthase; D005982:Glutathione Transferase; D004250:DNA Topoisomerases, Type II; D005978:Glutathione