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Important advance in understanding cause of brain cancer

Glioblastoma, the most common brain cancer of adults, carries a nasty prognosis, with patients typically living only six months after diagnosis if untreated and about a year and a half with the best available therapies.

So I was pretty hopeful a few years ago when I wrote this article in the Journal of the National Cancer Society about the discovery of an important biochemical mechanism that appeared to play a causal role in a large minority of glioblastoma cases: a mutation of a cell-surface molecule called EGFR. Based on this discovery, a vaccine that targets only cells carrying signs of the mutant molecule - and any cell that has this mutation is pretty much guaranteed to be a cancer cell, because of what the mutant molecule starts to do - went into the clinic several years back. Early trials showed very strong results. But in later-stage trials this vaccine's promising powers have dimmed.

Now we might know why: There's another genetic defect that turns out to be almost as common among glioblastomas as the first one is - and the two aberrations are virtually mutually exclusive, which means a glioblastoma patient's chances of having one or the other are better than even. As shown in this study, whose senior author is Stanford's Griff Harsh, MD, the newly identified genetic abnormality ultimately causes the same cancer-inducing biochemical events as the now more familiar one. And tumors are crazy-smart. They're dense Darwinian thickets that evolve rapidly because tumor cells divide relentlessly. So even if you nail one of the two gene aberrations with a great vaccine, some of those cells may pull an end-run by developing the other kind.

That's the bad news. The good news is: now we know. One of several of the study's implications is that, by combining attacks on both aberrations, it may be possible to wipe out tumors or at least beat them back to the point of converting this killer into a manageable chronic disease, as has been done with HIV. Perhaps academic scientists and pharmaceutical companies can put their heads together and find a way to make 1 plus 1 equal zero (zero tumor cells, that is).

From December 20 to January 3, Scope will be on a limited holiday publishing schedule. During that time, you may also notice a delay in comment moderation. We will return to our regular schedule on January 3.

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