Scientists have mapped the cascade of genetic changes that turn normal cells in the brain and pancreas into two of the most lethal cancers. The result points to a new approach for fighting tumors and maybe even catching them sooner.
Genes blamed for one person's brain tumor were different from the culprits for the next patient, making the puzzle of cancer genetics even more complicated.
But the research, also found that clusters of seemingly disparate genes all work along the same pathways. So instead of today's hunt for drugs that target a single gene, the idea is to target entire pathways that most patients share. Think of delivering the mail to a single box at the end of the cul-de-sac instead of at every doorstep.
The three studies, published today in the journals Science and Nature, mark a milestone in cancer genetics.
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“This is the next wave,” said Dr. Phillip Febbo of Duke University's Institute for Genome Sciences and Policy, who was not involved with the research. “What's really important is that finding those common elements within the landscape suggests there are therapeutic interventions that can help the whole group.”
Despite 30 years of work, scientists until now have found only a fraction of the genetic alterations required to cause any of the 200 diseases called cancer. Different tumors require a different domino effect of changes to arise, and to determine their severity and even which treatments will work.
The new maps do not include just mutated genes. They cite missing ones, extra ones, and overactive or underactive ones, in the most comprehensive look at human tumors.
Teams led by Johns Hopkins University examined more than 20,000 genes in tumors taken from 24 pancreatic cancer patients and 22 patients with the most dangerous brain tumor, called glioblastoma multiforme. Separately, The Cancer Genome Atlas project – a government-funded network of 18 medical centers – analyzed 600 genes in glioblastomas from 206 patients.
The Hopkins teams found hundreds of genetic changes, including a particularly intriguing gene named IDH1. Twelve percent of glioblastoma patients, mostly young ones, harbored a mutated version that brought longer survival: a median of 3.8 years compared with the 1.1 years for patients without the mutation.
The bigger discovery involved cancer's genetic chaos. No tumors were identical. The typical pancreatic cancer contained 63 genetic alterations and the average brain tumor 60, Hopkins researchers reported in Science.
Fortunately, “genes don't work alone,” said Hopkin's Dr. Kenneth Kinzler. Figure out which genes cluster in which pathways and “a simpler picture emerges.”