Sonic Hedgehog is required for small cell lung cancer progression

Lead researcher

Dr Anette Szczepny, Dr Jason Cain and Professor Neil Watkins

Main finding

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

Research group

Developmental and Cancer Biology


Anette Szczepny, Samuel Rogers, Samantha N. Jayasekara, Kwon Park, Rachael A. McCloy, Catherine R. Cochrane, Vinod Ganju, Wendy A. Cooper, Julien Sage, Craig D. Peacock, Jason E. Cain, Andrew Burgess, D. Neil Watkins.

Journal and article title

Most surprising

We found that Shh is capable of triggering canonical and, unexpectedly, non-canonical pathway activation by inducing cyclin B1 signalling leading to chromosomal instability.

Future implications

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.

Disease/health impact

Small cell lung cancer