title: [Chemotherapy agents, response rates and mechanisms of resistance in the therapy of the colorectal carcinoma].
abstract: Colorectal carcinoma is one of the most common cancers in Hungary, responsible for about 5000 deaths each year. In the first line treatment the most commonly used drugs are 5-fluorouracil, oxaliplatin and irinotecan. The most frequently used drug is 5-fluorouracil, which has no effect in 90% of the cases. In combination with leukovorin or with 5-ethyl-2'-deoxyuridin fluorouracil has an increased effect. The main mechanisms of the resistance against 5-fluorouracil are due to the overexpression of dihydropyrimidine dehydrogenase, MRP8, thymidylate synthase, and NFkB p65. Oxaliplatin forms reactive platinum complexes, which are believed to inhibit DNA synthesis by forming interstrand and intrastrand cross-linking of DNA molecules. The oxaliplatin-5-fluorouracil-leucovorin combination was the first to reach more than 20 months median survival. The main mechanisms of resistance are decreased accumulation, increased detoxification and increased DNA repair. Irinotecan inhibits the topoisomerase I enzyme, resulting in the inhibition of the repair of DNA breaks occurring during DNA synthesis. With sequential 5-fluorouracil, oxaliplatin, irinotecan combination 26 months median survival was reached. Mechanisms resulting in resistance are decreased accumulation, increased enzymatic detoxification, alterations of ABC transporters, DNA repair system, apoptotic pathways and topoisomerase I. Survival can be elongated using biological therapy (cetuximab, bevacizumab). In the near future biological therapy is expected to spread.
authors.affiliation: II. sz. Belgyógyászati Klinika, Semmelweis Egyetem, Budapest, Hungary.
authors.forename: Bálint
authors.initials: B
authors.lastname: Tegze
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Tulassay
authors.forename: Balázs
authors.initials: B
authors.lastname: Gyôrffy
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000068258:Bevacizumab; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D019496:Cancer Vaccines / Q000627:therapeutic use; D002277:Carcinoma / Q000188:drug therapy* / Q000453:epidemiology / Q000378:metabolism*; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000453:epidemiology / Q000378:metabolism*; D004260:DNA Repair / Q000187:drug effects; D004273:DNA, Neoplasm / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D006814:Hungary / Q000453:epidemiology; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D004273:DNA, Neoplasm; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000068258:Bevacizumab; D000077146:Irinotecan; D000068818:Cetuximab; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin