Beginning in 2001, some cancer patients receive targeted therapy – drugs that are prescribed to inhibit aberrant behaviour of proteins that promote the disease, rather than traditional treatments that systematically destroy dividing cells. Unfortunately, many of these patients eventually become insensitive to such targeted treatment because the tumour cells develop drug resistance through mutations of the proteins that make the drug targets. The mutant proteins are able to avoid binding the inhibitor while maintaining the function that is important for tumour growth. Here, I analysed such resistance mutations in three proteins that are drug-targets in cancers, by comparing their sequences to those of evolutionary-related proteins using state-of-the-art sequence alignment algorithms. The results show that the drug targets in fact have limited ability to undergo mutations. This finding is encouraging because it may mean that new drugs can be developed to target the mutants. However, computational and (independent) experimental evidence reveals that tumours can survive by developing additional mutations in the same gene.