Mesothelioma cases are on the rise, in both developed and developing countries. Thus, increased understanding of the underlying mechanisms of the disease is essential. Here, Dean Fennell, PhD, FRCP, of University Hospitals of Leicester NHS Trust, Leicester, UK, explains what he believes the key unanswered question in mesothelioma is. Prof. Fennel highlights the need to identify genetic vulnerabilities, equivalent to those provided by EGFR or ALK in lung cancer, to enable the precise targeting of the disease. This video was recorded at the British Thoracic Oncology Group (BTOG) Annual Conference 2018, held in Dublin, Ireland.