High levels of a protein known as Sonic hedgehog (SHH) may trigger certain forms of digestive tract tumour, according to two papers published online (Paper #1 and Paper #2) by Nature. Treatment with cyclopamine - a drug that inactivates SHH - can cause some tumours to shrink.
The Hedgehog signalling pathway specifies patterns of cell growth and development in a wide variety of embryonic tissues. High levels of activity are seen in many digestive tract tumours - including those originating in the oesophagus, stomach, biliary tract and pancreas - according to Philip A. Beachy and colleagues. In their study, mice carrying human biliary duct tumours responded to treatment with cyclopamine. Their tumours shrank completely after 12 days of treatment. In a second study, Sarah P. Thayer and colleagues report a similar effect of cyclopamine in mice with pancreatic tumours.
Both groups suspect that certain Hedgehog-related tumours are not caused by genetic mutation in the signalling pathway, rather they may be caused by high levels of a secreted molecule that activates the pathway. Thayer's team found that mice with high levels of one such molecule - known as Sonic hedgehog - developed abnormal tubular structures in their pancreata. These tumours resembled some early forms of human pancreatic cancer.
Collectively, both studies highlight the importance of the Hedgehog signalling pathway in certain digestive tract tumours. The pathway may have an early and critical role in cancer formation.
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