Sources of therapeutic failure: Difference between revisions
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*** EGFR mutation | *** EGFR mutation | ||
*** MET amplification | *** MET amplification | ||
** Anti-angiogenic therapy | |||
*** Switching expression to a new angiogenic factor not targeted by the drug | |||
*** Growth along existing blood vessels | |||
** Tamoxifen (and other selective estrogen modulating drugs) | ** Tamoxifen (and other selective estrogen modulating drugs) | ||
*** Loss of the estrogen receptor (domination by a clone that does not require ER) | *** Loss of the estrogen receptor (domination by a clone that does not require ER) | ||
Latest revision as of 04:57, 22 May 2008
The field of cancer drug resistance is pretty diverse, with causes ascribed to:
- Hypoxia
- if oxygen can't get to the cells, drugs might not either
- Oxygen is necessary for radiotherapy response
- Lack of the drug target (e.g., ER- cells in tamoxifen therapy)
- Density of the microenvironment - neoplasms and their surrounding matrix are often dense, and may impede drug diffusion.
- Upregulation of eflux pumps
- Methylation changes (not sure which yet)
- Genetic changes:
- Gleevec (Imatinib): BCR-ABL mutations
- 5-Flurouracil: TYMS amplification
- Gefitinib:
- EGFR mutation
- MET amplification
- Anti-angiogenic therapy
- Switching expression to a new angiogenic factor not targeted by the drug
- Growth along existing blood vessels
- Tamoxifen (and other selective estrogen modulating drugs)
- Loss of the estrogen receptor (domination by a clone that does not require ER)
- Upregulation of the estrogen receptor
- Constitutive activation of the estrogen receptor (rare in clinical samples)
- Mutant, hypersensitive ER