Investigation of circulating tumour DNA in the early detection of KRAS and EGFR mutant cancers

Work on the molecular mechanisms underlying the uncontrolled growth of tumours has identified many key regulatory proteins that are mutated in cancers. Clinically effective drugs have been developed targeting some of these proteins, such as the epidermal growth factor receptor (EGFR), but not for other commonly mutated cancer proteins, such as KRAS. However, despite these huge advances, the benefits of these targeted treatments in many advanced cancers tend to be temporary due to the development of drug resistance. By contrast, in common solid tumours where KRAS or EGFR mutations are frequent, such as those in the lung, pancreas and colon, early surgical intervention is by far the most effective therapeutic approach available. In order to diagnose cancer early to allow effective surgery, simple blood test-based assays would be hugely advantageous. 

We plan to study the ability of tumours to shed mutant DNA fragments into the circulating blood, using model systems to understand the mechanisms involved in this release. 

We hope this knowledge will lead to improved application of circulating tumour DNA analysis for cancer diagnosis and will investigate this in cohorts of individuals at risk of developing lung and other cancers.