Lung cancer is the second most common type of cancer in the UK, with 38,000 people being diagnosed each year. Biological therapies that target the epidermal growth factor (EGF) receptor are used to treat lung cancer in a subset of patients with EGF receptor mutations. These EGF receptor inhibitors, including afatinib, cetuximab, gefitinib and erlotinib, are associated with improved progression-free survival compared with chemotherapy. However, ultimately the tumours develop resistance, which often occurs due to further mutations in the EGF receptor.

In a new study published by BMC Medicine, Jacques De Grève and colleagues explore new strategies to overcome the problem of drug resistance, and show that interference with the EGF receptor gene using siRNA causes death of lung cancer cells. siRNA works by binding to a specific gene sequence in order to switch it off, preventing protein expression. The authors showed that siRNA was able to prevent lung cancer cell growth and cause death even in cells with resistance mutations in the EGF receptor. Importantly, siRNA enhanced the effects of afatinib, cetuximab, gefitinib and erlotinib, both in cells with and without resistance mutations. The strongest inhibition of cell growth was seen with a combination of siRNA and afatinib. 

The study unveils a potential new therapeutic approach to tackle drug-resistant lung cancer. Recent research has shown that siRNA therapy can be given to people and can prevent expression of specific genes, highlighting that a combination of EGF receptor inhibitors and siRNA is a feasible future therapy. The cell-based study by De Grève and colleagues reveals the exciting possibility of a drug-siRNA combination approach against lung cancer; future studies should extend these important findings into people and could confirm their therapeutic potential for drug-resistant lung cancer.