Dr Anette Szczepny, Dr Jason Cain and Professor Neil Watkins
We have identified a requirement for Sonic Hedgehog (Shh) ligand in the progression of small cell lung cancer using a well-characterised conditional mouse model. We show that mice with high levels of Shh develop highly aggressive tumours with marked chromosomal instability compared to mice lacking Shh. Our findings support an autocrine ligand-dependent mode of signalling in these tumours.
Centre for Cancer Research
Developmental and Cancer Biology
Journal and article title
We found that Shh is capable of triggering canonical and, unexpectedly, non-canonical pathway activation by inducing cyclin B1 signalling leading to chromosomal instability.
Despite preclinical evidence that the most commonly used Hedgehog pathway inhibitors, Smoothened antagonists, can inhibit the growth of a variety of common adult carcinomas, clinical trials of these agents in small cell lung cancer patients have proven disappointing. These findings shed light on why Smoothened inhibitors may not be effective in these lung cancer patients and suggest that the Shh ligand may be a potentially useful therapeutic target.
Small cell lung cancer