Breakthrough in understanding lung cancer vulnerabilities points the way to new targeted therapy

More effective treatments for one of the deadliest forms of cancer are one step closer thanks to groundbreaking research from an international collaborative study.

Scientists from the Universities of Sheffield and Cologne have identified the dependencies of multiple Small Cell Lung Cancer (SCLC) types – paving the way for clinical trials of new targeted treatments which could revolutionise the current approach.

Around 40,000 people are diagnosed annually with lung cancer in the UK, and SCLC accounts for nearly one in five of all these cases.

Unfortunately, the prognosis for SCLC patients is very bleak – two thirds of people are diagnosed in the late stages of the disease when the five year survival rate with current treatments is less than five per cent.

But now researchers have discovered that survival of SCLC cells grown from human tumours relies upon a protein called Aurora kinase.

This finding, published today (1 October 2012) in the journal: Proceeding of the National Academy of Sciences of the United States of America (PNAS), suggests that ‘targeted’ therapeutic strategies should focus on testing Aurora kinase inhibitors, several of which have already been developed by pharmaceutical companies.

The team also went on to show that Aurora kinase inhibitors are most effective at killing SCLC cells when the cells have high levels of the MYC cancer gene.

This predicts that these drugs might be most beneficial for SCLC patients with a MYC gene amplification, which is found in up to seven per cent of people diagnosed with SCLC.

Dr Patrick Eyers, from the University of Sheffield's Institute for Cancer Studies, said: "A major goal of modern cancer research is to discover drugs that target vulnerabilities in specific cancer patient sub-populations.

"Current chemotherapy for SCLC kills cancerous cells and non-cancerous cells indiscriminately and results in severe side effects.

"However, revolutionary clinical trials have recently validated ‘molecularly targeted’ kinase inhibitors for treating cancers such as melanoma, leukaemia and non-small cell lung cancer.

"We have been studying Aurora kinase inhibitors for several years, and the remarkable vulnerability of some SCLC-derived cells to such drugs can hopefully be rapidly confirmed by careful stratification of SCLC patients and their enrolment in new clinical trials.”

Additional information For more information about the study contact Dr Patrick Eyers on p.eyers@sheffield.ac.uk or visit http://www.shef.ac.uk/oncology/staffprofiles/peyers For the full paper visit http://www.pnas.org/content/early/recent The University of Sheffield

With nearly 25,000 students from 125 countries, the University of Sheffield is one of the UK’s leading and largest universities. A member of the Russell Group, it has a reputation for world-class teaching and research excellence across a wide range of disciplines. The University of Sheffield has been named University of the Year in the Times Higher Education Awards for its exceptional performance in research, teaching, access and business performance. In addition, the University has won four Queen’s Anniversary Prizes (1998, 2000, 2002, 2007). These prestigious awards recognise outstanding contributions by universities and colleges to the United Kingdom’s intellectual, economic, cultural and social life. Sheffield also boasts five Nobel Prize winners among former staff and students and many of its alumni have gone on to hold positions of great responsibility and influence around the world. The University’s research partners and clients include Boeing, Rolls Royce, Unilever, Boots, AstraZeneca, GSK, ICI, Slazenger, and many more household names, as well as UK and overseas government agencies and charitable foundations. The University has well-established partnerships with a number of universities and major corporations, both in the UK and abroad. Its partnership with Leeds and York Universities in the White Rose Consortium has a combined research power greater than that of either Oxford or Cambridge.