Understanding Lung Cancer

Among the various cancer forms, the deadliest type is lung cancer, comprised 80% of non-small cell lung cancer (NSCLC). Patients with advanced NSCLC have a 1-year survival rate of <10%. Conventional chemotherapy with cisplatin showed little efficacy. In recent years, insight into the signalling pathways regulating proliferation and survival of tumour has lead to molecularly targeted drug design. In its wake, kinase inhibitors like gefitinib and erlotinib have been developed and received fast-track approval by the FDA. In clinical studies, however, most patients treated with these EGFR inhibitors did not show a significant improvement over the placebo group.

Some patients, however, responded well to these drugs. Genetic sequencing revealed that these possessed an specific mutation in EGFR. Therefore, knowledge of the genetic lesions offers opportunities to select the drugs most effective on that particular tumour. To this date, there have been no comprehensive studies on the effect of kinase inhibitors on cancer cells with respect to their genetic profile.

In order to discover such oncogene-ligand pairs, we have screened over 1700 kinase inhibitors against 90 genet-ically annotated NSCLC cell lines harbouring clinically relevant mutations. We aim to understand how certain kinase inhibitors affect cells with specific genetic lesions.