Do beta-tubulin mutations have a role in resistance to chemotherapy?
beta-tubulin is the target of various antitubulin agents used in the treatment of cancer. After beta tubulin was shown to confer resistance to antitubulin agents in established cell lines, several studies have investigated the DNA sequence of this compound in clinical samples. However, these findings are highly controversial, since sequencing experiments showed that the original clinical observation of mutations in the gene resulted from inclusion of non-functional beta-tubulin pseudogenes. At least nine such pseudogenes are known, and all share substantial sequence homology with the functional gene. Subsequent studies have concluded that beta-tubulin mutations in clinical samples are rare, and unlikely to contribute to drug resistance. Here, we overview the beta-tubulin gene family and summarise the results of studies done comparing beta-tubulin mutations with antitubulin drug resistance.
Berrieman
Helen K
HK
Postgraduate Medical Institute, University of Hull, UK. H.K.Berrieman@medschool.hull.ac.uk
Lind
Michael J
MJ
Cawkwell
Lynn
L
D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D006801:Humans; D009154:Mutation / Q000235:genetics*; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D011544:Pseudogenes / Q000235:genetics*; D014404:Tubulin / Q000235:genetics*
D000970:Antineoplastic Agents; D014404:Tubulin