Arul Chinnaiyan kicked off the day for AACR’s 101st annual meeting in DC by talking about cancer genomes. He gave a roundup of some of the major genomes published to date, many of them in Nature. He even showed a brilliant screenshot of Heidi Ledford’s April 15 feature on the topic. Bert Vogelstein of Johns Hopkins followed up with a talk that seemed too good to be true, asserting that thanks to decades of research, cancer is essentially a known entity. He’s been comparing the genomic landscape of nearly 100 human cancer genomes that have been sequenced to date and other data to come up with 3142 genes that are mutated regularly. He applies a simple criteria to distinguish which of these three thousand genes likely suppress tumor formation as their usual function (a function which a mutation disrupts), and those that through mutation become more active and cause cancer (so-called oncogenes).
Where more than 15% of the mutations catalogued by genome projects look like truncating mutations — those that would screw up the protein it encodes — he assumes it’s a tumor suppressor. He found 286 of these. When exactly the same part of the gene is mutated in at least two different tumors – meaning that a very specific mutation appears necessary – he calls it an oncogene. He found 33 of these.
These 320 genes fall roughly into 12 core biological pathways and understanding these pathways better should lead to better cures.
It sounds so simple: “We really kind of understand cancer, now,” he says. The caveat, or “the elephant in the room” as he calls it is that cancers are still very heterogeneic resisting a singular approach to a cure. And the fact that 90% of cancer genes are tumor suppressors poses a challenge. They’re harder to act upon with inhibitory drugs.
Some may argue his point that life, or cancer, is so simple. In fact, at a session later on nanotechnology Anna Barker of the National Cancer Institute, urged participants to embrace the complexity of cancer. “Complexity is our friend,” she says. Reminds me of Erika Check Hayden’s feature from April 1.