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 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.
Volm
M
M
Department of Oncological Diagnostics and Therapy, German Cancer Research Center, Heidelberg, Germany.
Mattern
J
J
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
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