hey - just want clarification. I thought TKIs like gleevec give an asymptomatic period of years - do you mean by "develop resistance" the initial seed population of cells that are resistant emerge from a (presumably clonal or near-clonal) pool within months?
Second: Do you know if clinically, agents like gleevec are primarily used as standalone or in conjunction with more aggressive (and, unfortunately, side-effect laden) therapies? I was always a bit aware of the pernicious "maintenance drug" status of gleevec, but presumably if you combine it with an orthogonal therapy you could get higher coverage and better statistical odds of sending the patient into remission.
Imatinib and other TKIs provide a range of effectiveness, from weeks/months to years. Nothing is forever (although the CD1 Ligands like ipilimumab etc show promise).
Mostly, the TKIs spread the Kaplan-Meyer curve out/lengthen it, but because it is still relying on the immune system to kill the cells (mostly) essentially TKIs are providing cellular senescence rather than cellular death. The bcr/abl mutation that imatinib targets is a cellular replication pathway, not s cell death pathway
Second: Do you know if clinically, agents like gleevec are primarily used as standalone or in conjunction with more aggressive (and, unfortunately, side-effect laden) therapies? I was always a bit aware of the pernicious "maintenance drug" status of gleevec, but presumably if you combine it with an orthogonal therapy you could get higher coverage and better statistical odds of sending the patient into remission.