Here’s a gauntlet thrown down – let’s see how many people show up to the duel. Vinay Prasad has a piece in Nature titled “The Precision Oncology Illusion”, with the subhead saying “Precision oncology has not been shown to work, and perhaps it never will”. (Here’s Prasad earlier this year, with co-authors in The Lancet on the same theme).
To get the definitions straight, by “precision oncology” he means (rightly) the idea of using DNA sequence information from individual patients to tailor what therapy they should get. (Keep in mind that there are a lot of stories in the popular press that have garbled that idea a bit over the years, and there are a lot of press releases that name-check it without having much connection to it at all – the signal/noise isn’t that great). Now, that idea would seem to make very good sense, because it’s become abundantly clear over the years that every tumor is slightly different when looked at on a genetic level. So what’s Prasad’s problem?
For one thing, we just don’t have many targeted therapies to offer yet. It’s gotten easier and easier to sequence human tissue, but it has not gotten correspondingly easier – to put it gently – to match that result with a therapy that’s been shown to have better outcomes. Prasad has some unsetting figures on this, especially for solid-tumor patients. In that area, he says that he has been able to find only 32 reports of exceptional responses over the years after sequencing and targeted therapy, and even many of these don’t seem to hold up as well as they should on closer inspection. In the big oncology picture, there aren’t many of those at all, so for most patients (arguably “nearly all patients”) there really isn’t a targeted therapy to offer. That problem, though, could in theory resolve itself over the years with a lot more work in the clinic (and a lot more oncology agents coming out of the labs). That’s not an easy fix, but the other problems may be even harder to deal with.
As Prasad mentions, one big problem is that even when you find a particular mutation that would seem to make a tumor susceptible to a targeted therapy, it often doesn’t seem to do any good. The mutation is present, but it’s not the thing driving the tumor’s growth, and most of the time there’s no good way to tell that up front. (See this report from a couple of months ago as an example). Other (even bigger) obstacles that Prasad doesn’t have the space to go into are the genetic diversity of most tumors (you’re not fighting a single cell type with a single set of mutations) and the mutation rates themselves. Too often, especially for many solid tumors, what we end up doing is allowing patients to die, a few weeks or months later, from another subset of their tumor cells after we have cleared the way by eliminating the cellular competition. That’s not a very nice way to put things, but from what I can tell, that’s about the size of it (I’m well aware that those extra few weeks or months may well be worth a lot, depending on what they’re like and on the patient’s own situation). Many people are aware that this is the situation, but my worry is that they associate this state of affairs with old-fashioned chemotherapy, not that new precision DNA-targeted therapy that you hear about. But the same thing is going to happen for many of those, too.
That’s a real problem. You have a lot of cancer treatment centers advertising their ability to tailor a therapy right for you, the patient, with cutting-edge techniques that have recently become available. Except that these mostly don’t exist yet, and mostly aren’t applicable to the people who show up for treatment, and may not (for the reasons given above) ever exist for some (many?) patients at all. This field has been proclaimed as the coming thing for many years now – fine. But proclaiming it as already having arrived is not a good move.