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Resistance in the land of molecular cancer therapeutics.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Shannon, Kevin M. |
| Copyright Year | 2002 |
| Abstract | The fusion tyrosine kinase Bcr-Abl plays a fundamental role in the pathogenesis of chronic myeloid leukemia (CML). Imatinib, a potent inhibitor of Bcr-Abl, has shown impressive clinical activity in CML patients. However, primary and acquired resistance occurs in many patients and is associated with reactivation of Bcr-Abl in primary leukemia cells. Studies reported over the past year have begun to elucidate the molecular basis of imatinib resistance, which may involve amplification of BCR-ABL or, more commonly, mutations that introduce amino acid substitutions into the Bcr-Abl kinase. Biochemical analysis and molecular modeling indicate that these mutant proteins retain kinase activity but are less sensitive to inhibition due to structural changes that perturb drug binding. These studies establish a paradigm for elucidating resistance to targeted therapeutics. |
| Starting Page | 99 |
| Ending Page | 102 |
| Page Count | 4 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.biolchem.ucla.edu/labs/Tim_Lane/CourseMBI297PTKmaterials/PTKfiles/Wk7REV_Shannon2002.pdf?origin=publication_detail |
| PubMed reference number | 12204529v1 |
| Volume Number | 2 |
| Issue Number | 2 |
| Journal | Cancer cell |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Abetalipoproteinemia Amino Acid Substitution Amino Acids B-Cell Receptor Complex Fusion Proteins, bcr-abl Mutation Myeloid Leukemia Myeloid Leukemia, Chronic Patients Protein Tyrosine Kinase Therapeutic brand of coal tar Therapeutic procedure imatinib kinase activity molecular modeling |
| Content Type | Text |
| Resource Type | Article |
