Fig. 1.

Relationship between microtubule polymer levels and drug resistance. The model assumes that cells remain viable within a small range of polymer levels denoted by the dashed lines, but they experience toxicity (failure to divide) outside of that range. Drugs like colcemid (Cmd) become toxic at concentrations that lower polymer levels beneath the lower limit; drugs like paclitaxel (Ptx) become toxic at concentrations that raise polymer levels beyond the upper limit. Drug resistance mutations move the polymer levels in a direction that opposes the selecting drug (paclitaxel resistance (Ptx^R) to lower levels; colcemid resistance (Cmd^R) to higher levels). When the mutations are strong enough to move the polymer levels into the toxic zones, drug dependence (Ptx^D; Cmd^D) occurs.