From Nature comes this news of an effort to go back to oncology clinical trials and look at the outliers: the people who actually showed great responses to otherwise failed drugs.
By all rights, Gerald Batist’s patient should have died nine years ago. Her pancreatic cancer failed to flinch in the face of the standard arsenal — surgery, radiation, chemotherapy — and Batist, an oncologist at McGill University in Montreal, Canada, estimated that she had one year to live. With treatment options dwindling, he enrolled her in a clinical trial of a hot new class of drugs called farnesyltransferase inhibitors. Animal tests had suggested that the drugs had the potential to defeat some of the deadliest cancers, and pharmaceutical firms were racing to be the first to bring such compounds to market.
But the drugs flopped in clinical trials. Companies abandoned the inhibitors — one of the biggest heartbreaks in cancer research over the past decade. For Batist’s patient, however, the drugs were anything but disappointing. Her tumours were resolved; now, a decade later, she remains cancer free. And Batist hopes that he may soon find out why.
That's a perfect example, because pancreatic cancer has a well-deserved reputation as one of the most intractable tumor types, and the farnesylation inhibitors were indeed a titanic bust after much anticipation.. So that combination - a terrible prognosis and an ineffective class of compounds - shouldn't have led to anything, but it certainly seems to have in that case. If there was something odd about the combination of mutations in this patient that made her respond, could there be others that would as well? It looks as if that sort of thing could work:
Early n-of-1 successes have bolstered expectations. When David Solit, a cancer researcher also at Memorial Sloan-Kettering, encountered an exceptional responder in a failed clinical trial of the drug everolimus against bladder cancer, he decided to sequence her tumour. Among the 17,136 mutations his team found, two stood out — mutations in each of these genes had been shown to make cancer growth more dependent on the cellular pathway that everolimus shut down1. A further search revealed one of these genes — called TSC1 — was mutated in about 8% of 109 patients in their sample, a finding that could resurrect the notion of using everolimus to treat bladder cancer, this time in a trial of patients with TSC1 mutations.
So we are indeed heading to that dissection of cancer into its component diseases, which are uncounted thousands of cellular phenotypes, all leading to unconstrained growth. It's going to be quite a slog through the sequencing jungle along the way, though, which is why I don't share the optimism of people like Andy von Eschenbach and others who talk about vast changes in cancer therapy being just about to happen. These n-of-1 studies, for example, will be of direct benefit to very few people, the ones who happen to have rare and odd tumor types (that looked like more common ones at first). But tracking these things down is still worthwhile, because eventually we'll want to have all these things tracked down. Every one of them. And that's going to take quite a while, which means we'd better get starting on the ones that we know how to do.
And even then, there's going to be an even tougher challenge: the apparently common situation of multiple tumor cells types in what looks (without sequencing) like a single cancer. How to deal with these, in what order, and in what combinations - now that'll be hard. But not impossible and "not impossible" is enough to go on. Like Francis Bacon's "New Atlantis", what we have before us is the task of understanding ". . .the knowledge of causes, and secret motions of things; and the enlarging of the bounds of human empire, to the effecting of all things possible". Just don't put a deadline on it!