Abstract: The invention relates to methods for determining resistance or responsivity to microtubule-targeting drug treatment in cancer patients. The methods comprise obtaining a tumor cell sample from a cancer patient and analyzing DNA in the tumor cell sample to determine the presence or absence of a loss of heterozygosity (LOH) at the M40 ?-tubulin gene locus within chromosomal locus 6p25, where determining LOH comprises screening for at least one mutation in the M40 ?-tubulin gene that affects the binding of a microtubule-targeting drug to ?-tubulin. In such methods, the presence of LOH is indicative of microtubule-targeting drug resistance in the cancer patient or of a decreased likelihood that the cancer patient will respond to therapy with a microtubule-targeting drug.