Novel Biomarkers and Drug Targets in Non-Small Cell Lung Cancer

Abstract

Despite therapeutic advances, the prognosis of non-small cell lung cancers (NSCLC) is still very poor, especially when first diagnosed at later stages involving metastases. NSCLC classification can be aided by identifying genetic, molecular, and histological subtypes that are important biomarkers in treatment selection. The majority of targeted therapies are now first-line treatment options for eligible patients with advanced stages of NSCLC. Here they have been shown to improve overall survival (OS) and progression free survival (PFS). Such treatments include those aimed at driver mutations in NSCLC, such as the genes for EGFR and ALK, and immune checkpoint inhibitors such as those targeting programmed death protein 1 or its ligand (programmed death ligand 1 [PD-L1]). In antibody-drug conjugates (ADC), cytotoxic payloads are conjugated to monoclonal antibodies (mAb) that deliver the drug to tumour cells expressing the corresponding target antigen. While there are still no ADCs specifically approved for NSCLC by the U.S. Food and Drugs Administration (FDA), several agents have shown promise and are being investigated as therapy in NSCLC. Emerging biomarkers as targets for ADCs with potential relevance in the treatment of NSCLC include products of the genes CEACAM5, TROP2, HER2, and c-MET. Herein, this interview provides an overview of biomarkers and targeted therapies, with a discussion with Grace Dy, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA, on their potential clinical utility.