You may have detected, here and there, a certain amount of skepticism on this blog about the direct application of genomic information to complex human diseases. And several times I’ve beaten the drum for the position that there is no such disease as “cancer” – just a lot of conditions that all result in the phenotype of uncontrolled cellular growth.
Well, here’s some pretty dramatic evidence in favor of both of those positions. A new study, one of those things that could only be done with modern sequencing techniques, has given us the hardest data yet on the genomic basis of cancerous cells. This massive effort completely sequenced the tumors from 50 different breast cancer patients, along with nearby healthy cells as controls for each case.
Over 1700 mutations were found – but only three of them showed up in as many as 10% of the patients. The great majority were unique to each patient, and they were all over the place: deletions, frame shifts, translocations, what have you. The lead author of the study told Nature News that the results were “complex and somewhat alarming”, and I second that, only pausing to drop the “somewhat”. I add that qualification because these patients were already more homogeneous than the normal run of breast cancer cases – they were all estrogen-receptor positive, picked for trials of an aromatase inhibitor.
Half the tumors were estrogen-sensitive, and half weren’t, and one of the goals of the study was to see if any genetic signatures could be found that would distinguish these patients. There was an association with the MAP3K1 gene, but hardly a powerfully predictive one, since that one only showed up in 10% of the samples to start with. (Mind you, that still makes it one of the top three mutations).
The Nature piece contains some brave-face material about how this study has uncovered a whole list of new therapeutic targets, but sheesh. What are the odds that any of these will prove to be crucial, even for the low percentage of women who turn out to have them? No, instead of making me yearn for ever-more-personalized targeted therapies, this makes me think that early detection and powerful, walloping chemotherapy (and surgery) must be the way to go for now. I mean, this was still only fifty patients, and uncovered this much complexity: how tangled must the real world be?
We’ll get a chance to start finding out – the same team is now moving ahead to expand this effort to 1,000 patients. These are also, I believe, from clinical trials, so we’ll be able to correlate outcomes with exact genetic sequences. If there are any correlations that we can understand, that is. . .that’s the next thing that I’m really looking forward to seeing. If the whole personalized-medicine idea is ever to work, this is just the sort of thing that’s going to have to be done. But we shouldn’t be surprised if the results, for some time to come, are that the whole era of personalized medicine is a lot further away than we might have thought.