Over the last few years, there's been more attention paid to a problem in cancer therapy that is going to keep us all very busy: drug resistance. Everyone's heard about this topic in reference to antibiotics, and with good reason. But the same thing happens in oncology, which makes sense. Despite a lot of major differences, in both cases we're trying to kill off robust, fast-dividing cells that have a lot of genetic variation in them. Anything that doesn't respond to the drug is going to have an open field in front of it.
The situation in cancer might actually turn out to be worse than in antibiotics, disturbing though that sounds. For one thing, cancer cell lines are often rather genetically unstable, which may well be how they ended up becoming cancer cell lines in the first place. So mutants are pretty easy to come by. Counterbalancing that, they don't have a quick way of transferring genetic material to each other like bacteria do, which means that we don't have to restrict the use of the therapies like we have to with antibiotics. Each patient is an island, fortunately.
The real difficulty is that antibiotics are typically taken for a set course of treatment - you knock the infection down enough to where the patient's immune system can clean up the rest, and everything's done. But cancer therapies, the kind that we're turning out now, are likely going to be more like insulin is for diabetics - you're going to be taking them for a long time, quite possibly for the rest of your life, which gives plenty of time for something bad to happen. It's impossible to know whether all the cancer cells disappear, or whether they're just lying low. So no one's sure yet what will happen ifyou go off of the drugs, and as you can imagine, that's data which is going to be hard to obtain.
Gleevec (imatinib) is a good example. There are all too many patients who have taken the drug for longer periods and have seen it lose its effectiveness, which must be really a wrenching experience. The kinase that the drug targets (Bcr-Abl) turns out to have a number of mutant forms that are unaffected by Gleevec, so any cells that have (or develop) these variants are free to cut loose. Interestingly, it may be the case that Bcr-Abl itself sets up conditions inside the cell that favor development of mutations, which for cancer cells could be something of a survival tool.
The only way around such problems is to make new drugs, just like in the antibiotic field. Two of the most advanced ones are AMN107 (nilotinib) and BMS354825 (dasatinib). Dasatinib had a good ASCO meeting, with an FDA committee recommending its approval, and with new data being presented comparing it head to head with Gleevec. So far, it looks like it's superior to higher doses of Gleevec in CML patients who've started to show resistance, but this is all with blood markers (as opposed to real survival data, which naturally takes longer to come in). But so far, so good.
These might remain useful for longer, since their binding modes are somewhat different than Gleevec, and whole classes of mutant Bcr-Abl forms are still susceptible. But resistance will surely keep cropping up. We're going to be a this for a long time.