From platinum compounds to targeted therapies in advanced thoracic malignancies

Improved understanding of the molecular mechanisms involved in development, growth and spread of cancer have led to develpment of targeted therapies for many cancers. Based on their superior tolerability and efficacy, targeted therapies with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) or crizotinib are preferred first-line treatments over platinum-based chemotherapies in patients whose tumours harbour EGFR-activating mutations and anaplastic lymphoma kinase (ALK) translocations, respectively. Active areas of research in EGFR-mutant and ALK-translocated NSCLC include identification of mechanisms of resistance and overcoming them. Therapeutic targeting of several other targets including ROS, RET and discoidin domain receptor 2 (DDR2) tyrosine kinases are in early phases of clinical evaluation. Despite the advances in tumour genomic sequencing, a substantial fraction of patients with non-small cell lung cancer (NSCLC) do not have any targetable genetic alteration. Ongoing research is focused on identifying mechanisms of carcinogenesis in these patients. Targeted therapies in small cell lung cancer (SCLC) and thymic malignancies have not yielded meaningful clinical benefits, and platinum-based therapies remain the cornerstone of treating patients with advanced disease.