KRAS mutations are found in around 30 percent of lung adenocarcinomas, the most common type of lung cancer.
Until recently, mutant KRAS lung cancers were seen as a single disease sub-group, usually treatment-resistant. But a study led by Dr Carla Martins (MRC Cancer Unit) and published in Nature now shows that mutant Kras lung tumours are a heterogeneous group comprising two classes of tumours with distinct metabolic profiles, prognosis and therapeutic susceptibilities.
By comparing lung tumour cell lines and murine lung tumours with a single copy of mutant KRAS against those with two or more mutant alleles, the authors showed that those with extra mutant copies are more aggressive and exhibit unique metabolic features, which help them survive, making them more likely to spread. But importantly, this study also shows that these aggressive tumours have unique metabolic needs that can be exploited therapeutically.
This work suggests that the heterogeneity of these tumours may have contributed to their poor treatment responses and that combined quantitative and qualitative KRAS locus assessment may have both prognostic and therapeutic utility.