Establishment of an ex vivo precision-cut lung slice model for the evaluation of drug-radiation responses

Our research focuses on lung cancer where our primary aim is to identify new drug targets and to determine how best to integrate novel therapies with current standards of care in lung cancer, and to optimise combination treatments including radiation therapy.
During its development, lung cancer acquires activating mutations that are critical for continued tumour growth. For example, recurrent mutations have been described in several key oncogenes (including EGFR, KRAS, ALK, BRAF, PIK3CA and ERBB2). Since these activating mutations are not found in normal tissues, we are currently screening for combinations of novel compounds that can selectively kill these cells while leaving normal cells unaffected.

Importantly, lung cancer can also acquire loss of function mutations in tumour suppressor genes. As a consequence, tumour cells can become highly dependent on compensatory signalling pathways, which might then be targeted in order to kill the tumour cells. In contrast, non-tumour cells without the tumour suppressor gene mutation, are less dependent on these compensatory pathways and therefore are relatively unaffected by pathway inhibition. We are currently screening for targets and compounds that can lead to selective killing of cells with tumour suppressor gene mutations that are common in lung cancer (e.g. TP53, LKB1, ATM).