Update on molecular pathology and role of liquid biopsy in nonsmall cell lung cancer

Personalised medicine, an essential component of modern thoracic oncology, has been evolving continuously ever since the discovery of the epidermal growth factor receptor and its tyrosine kinase inhibitors. Today, screening for driver alterations in patients with advanced lung adenocarcinoma as well as those with squamous cell carcinoma and no/little history of smoking is mandatory. Multiplex molecular platforms are preferred to sequential molecular testing since they are less time-and tissue-consuming. In this review, we present the latest updates on the nine most common actionable driver alterations in nonsmall cell lung cancer. Liquid biopsy, a simple noninvasive technique that uses different analytes, mostly circulating tumour DNA, is an appealing tool that is used in thoracic oncology to identify driver alterations including resistance mutations. Additional roles are being evaluated in clinical trials and include monitoring the response to treatment, screening for lung cancer in high-risk patients and early detection of relapse in the adjuvant setting. In addition, liquid biopsy is being tested in immune-oncology as a prognostic, predictive and pharmacodynamic tool. The major limitation of plasma-based assays remains their low sensitivity when compared to tissue-based assays. Ensuring the clinical validity and utility of liquid biopsy will definitely optimise cancer care.