Clinical Resistance to STI-571 Cancer Therapy Caused by BCR-ABL Gene Mutation or Amplification

@article{Gorre2001ClinicalRT,
  title={Clinical Resistance to STI-571 Cancer Therapy Caused by BCR-ABL Gene Mutation or Amplification},
  author={Mercedes E. Gorre and Mansoor S. Mohammed and Katharine Ellwood and N Hsu and Ronald L. Paquette and P Nagesh Rao and Charles L. Sawyers},
  journal={Science},
  year={2001},
  volume={293},
  pages={876 - 880}
}
Clinical studies with the Abl tyrosine kinase inhibitor STI-571 in chronic myeloid leukemia demonstrate that many patients with advanced stage disease respond initially but then relapse. Through biochemical and molecular analysis of clinical material, we find that drug resistance is associated with the reactivation of BCR-ABL signal transduction in all cases examined. In six of nine patients, resistance was associated with a single amino acid substitution in a threonine residue of the Abl… 
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TLDR
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TLDR
Molecular mechanisms of TKI resistance paying particular attention to drug resistance which allows for a survival advantage in CML are presented.
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TLDR
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TLDR
It is shown that the farnesyl transferase inhibitor (FTI) SCH66336 (lonafarnib) inhibits the proliferation of STI571- resistant BCRABL–positive cell lines and hematopoietic colony formation from peripheral blood samples of STi571-resistant patients with CML.
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