Paclitaxel Resistance in Non–Small-Cell Lung Cancer Associated With Beta-Tubulin Gene Mutations

We have identified beta-tubulin gene mutations as a strong predictor of response to the antitubulin drug paclitaxel; these mutations may represent a novel mechanism of resistance and should be examined prospectively in future trials of taxane-based therapy in non–small-cell lung cancer

Mariano Monzó

2017

Scholarcy highlights

  • The mechanisms that cause chemoresistance in non–small-cell lung cancer patients have yet to be clearly elucidated
  • We reasoned that polymerase chain reaction and DNA sequencing of the beta-tubulin gene could reveal more information regarding the connection between beta-tubulin mutations and primary paclitaxel resistance
  • PATIENTS AND METHODS: Constitutional genomic DNA and paired tumor DNA were isolated from 49 biopsies from 43 Spanish and six American stage IIIB and IV NSCLC patients who had been treated with a 3-hour, 210 mg/m2 paclitaxel infusion and a 24-hour, 200 mg/m2 infusion, respectively
  • Oligonucleotides specific to beta-tubulin were designed for PCR amplification and sequencing of guanosine triphosphate- and paclitaxel-binding beta-tubulin domains
  • None of the patients with beta-tubulin mutations had an objective response, whereas 13 of 33 patients without beta-tubulin mutations had complete or partial responses
  • We have identified beta-tubulin gene mutations as a strong predictor of response to the antitubulin drug paclitaxel; these mutations may represent a novel mechanism of resistance and should be examined prospectively in future trials of taxane-based therapy in NSCLC

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