Expression of Oncogenic Epidermal Growth Factor Receptor Family Kinases Induces Paclitaxel Resistance and Alters β-Tubulin Isotype Expression

De novo or acquired resistance to chemotherapeutic agents can be induced by increased clearance mediated by membrane transporter proteins or by modification of molecular targets

R.Bruce Montgomery

2002

Scholarcy highlights

  • De novo or acquired resistance to chemotherapeutic agents can be induced by increased clearance mediated by membrane transporter proteins or by modification of molecular targets
  • As a model system that mimics these effects, we determined the effect of EGFR expression on sensitivity to paclitaxel in transfected fibroblast cell lines
  • Cells expressing the EGFR mutant and HER2 were 2–3-fold more resistant to paclitaxel compared with the parental cell line
  • This level of resistance is modest compared with that induced by selection in tubulin-active agents, but it correlates well with other parameters of oncogenicity associated with expression of EGFRvIII, such growth in serum-free medium
  • Resistance to antineoplastic agents can be mediated by many different mechanisms, including differential uptake and retention of drug controlled by membrane transporter proteins
  • EGFR and HER2 overexpression is inversely correlated with response to chemotherapy and prognosis, and resistance is often accompanied by an increase in receptor expression
  • Antisense oligonucleotides specific to isotype class III b-tubulin are capable of blocking class III expression while reversing taxane resistance in drug-resistant lung carcinoma cells

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