胰腺癌基因讯息途径被揭开

The National Cancer Institute estimates that more than 43,000 Americans were diagnosed with pancreatic（胰腺的） cancer last year and more than 36,000 died from the disease. Despite advances in genetic¹ science showing that the Ras oncogene（致癌基因） is mutated in virtually all pancreatic cancers, scientists have been frustrated² by the complexity³ of the signaling pathways in humans, which make it difficult to pinpoint⁴ potential therapeutic⁵ targets. In a study published today in the Cell Press journal Developmental Cell, a team of researchers led by Channing Der, PhD, Distinguished⁶ Professor of Pharmacology at UNC-Chapel Hill, took a step back to a simpler organism – a common roundworm（蛔虫） – and made a discovery about how the Ras oncogene chooses a signaling pathway and how the consequences of that choice play out in cellular⁷ development – a key issue in cancer, which is characterized by uncontrolled cell growth.

Der, who is also a member of UNC Lineberger Comprehensive Cancer Center, explains, "In humans the cell signaling pathways are very complex; there are more than 20 different downstream partners beyond the two proteins we study – Raf and RalGEF – that Ras can choose to interact with. In C. elegans, there is only one of each protein. That made it easier for us to identify how Ras chooses a partner to 'dance' with and what are the critical events in the subsequent cell development that promote cancer."

"We found an elegant mechanism⁸ by which Ras switches partners and showed that the choice leads to very different fates for the cell. Now we can go back to the human pancreatic cancer cell and ask whether similar mechanisms⁹ are at work in determining how Ras causes pancreatic cancer," he adds.

Scientists often study simpler organisms to tease out（梳理） genetic and cellular activity that might be almost impossible to map in humans. "Worms' cells actually share a great deal of functional¹⁰ overlap¹¹ with human cells. However, while there may be one mechanism in a simple organism like a worm, there are multiple mechanisms at work in humans. It's a great thing for us as people, because there is a great deal of redundancy（冗陈） in our biological systems that helps them self-repair and function better, but it makes it a lot harder to study what's going on at a basic level," Der notes.

"If this signaling works in a similar way in humans, the C. elegans（线虫） model may be very powerful for helping¹² us find new therapeutic targets for pancreatic cancer," he concludes.