Drug resistance in lung cancer

Jozef Škarda, Marian Hajdúch, Patrik Flodr, Eduard Fridman, Juri Kopolovic, Vítězslav Kolek, Jiří Klein, Zdeněk Kolář

Research output: Contribution to journalArticlepeer-review

Abstract

Drug resistance is an important problem in the treatment of patients with cancer. Tumors become resistant not only to the drugs used initially, but also to those to which they have not yet been exposed. Data obtained from various sources indicate that multiple mechanisms contribute to drug resistance. Many of them are mutually related to each other. Resistance-related proteins such as P-glycoprotein, multidrug resistance related protein, lung resistance related protein, glutathione-dependent enzymes, topoisomerases, metallothioneins, thymidylate synthase and O6-alkylguanine-DNA alkyltransferase have been found in different human lung tumors, but these alone cannot explain the drug-resistant phenotype. Cell-cycle-related proteins, angiogenic-factors, protooncogenes, and tumor suppressor genes can also contribute to the manifestation of drug resistance phenotypes. In future, a key challenge will be to determine the relative quantitative contributions of each of these mechanisms to overall resistance. The use of DNA microarray technology will yield insight into the mechanisms of drug resistance and facilitate the rational design of more effective strategies to circumvent resistance.

Original languageEnglish
Pages (from-to)545-570
Number of pages26
JournalPharmacologyonline
Volume3
StatePublished - 2007

Keywords

  • DNA microarray
  • Drug resistance
  • Lung cancer
  • Protooncogenes
  • Resistance-related proteins

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