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Existing Cancer Treatment Could be Used for Common ‘Untreatable’ Form of Lung Cancer

publication date: Jul 13, 2018
 | 
author/source: University of Glasgow

University of GlasgowA cancer treatment already approved for use in certain types of cancer has been found to block cell growth in a common form of lung cancer for which there is currently no specific treatment available.

The new findings, published today in Science Translational Medicine and led by the University of Glasgow, suggest that a large number of patients could benefit from this treatment – a second generation EGFR inhibitor (a drug that slows down or stops cell growth) – if used in combination with additional therapies.
 
The scientists hope the treatment could be deployed for use in patients in the near future, given it is already approved for the treatment of other cancers.
 
Cancers of the lung kill more people worldwide than cancers of any other organ, more than 1.5m people per annum. The largest subtype of lung cancer, which the researchers studied, is adenocarcinoma.
 
One third of adenocarcinoma cancers carry a mutant gene called KRAS, which the researchers show requires the activity of any of four ‘EGFR/ERBB growth factor receptors’ to drive cell proliferation. There are presently no KRAS-inhibiting drugs available for treatment of these cancers and first generation EGFR drugs have failed to show any benefit to this form of cancer.
 
However, the scientists in this study found that, unlike first-generation EGFR inhibitors, one particular second-generation EGFR inhibitor – a multi-ERBB inhibitor - blocked the proliferation of KRAS-mutant lung cancer cells in lab studies and actually prevented the formation of KRAS-driven lung cancers in mice.
 
Lead author Dr Daniel Murphy, Senior Lecturer at the University’s Institute of Cancer Sciences and a scientist at Glasgow’s Cancer Research UK Beatson Institute, said: “There is a pressing need to develop alternative strategies for more effective treatment of KRAS‐driven lung cancer, and this is a promising breakthrough which we hope could benefit patients soon.
 
“The inhibitor we studied – a multi-ERBB inhibitor – helped sensitise tumours and was of therapeutic benefit when used in combination with another cancer drug called Trametinib, resulting in a clear extension of lifespan.
 
“Based on our findings, we hope lung cancer patients with the KRAS-driven form of lung cancer may in future benefit from inclusion of this inhibitor in their treatment plan.”
 
Unwanted side-effects of these drugs on normal tissues remains a concern, however, new strategies to limit delivery of these drugs to the tumour site could reduce such side-effects and greatly improve the utility of this class of therapeutics.
 
The paper, ‘The ERBB network facilitates KRAS-driven lung tumorigenesis,’ is published in Science Translational Medicine. The work was funded by a MINT
Collaborative grant from Merck Sharpe & Dohme; a Deutsche Krebshilfe grant; and grants from the European Commission Marie Curie Actions and the British Lung Foundation in collaboration with the Scottish Government Chief Scientist Office.




 

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