University Clinic Golnik, Medical Oncology Unit, Szlovénia
Lung cancer is the leading cause of cancer related deaths thus presenting one of the main public health related issues globally. Non-small cell lung cancer (NSCLC) represents approximately 85% of all lung cancer cases. Historically, platinum-based chemotherapy was the mainstay of systemic therapy for NSCLC, leading to median survival rates of only 8 to 10 months. Major improvement in the treatment of NSCLC was made through the identiﬁ cation of key genetic aberrations (oncogene drivers) that drive tumor initiation, maintenance and progression and development of highly effective oncoge- ne-directed therapies. Oncogene-directed therapies against epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) in conjunction with well-validated methods for the detection of their targets already represent a standard care of advanced NSCLC patients. Encouragingly, in the recent years a number of additional genetic aberrations have emerged as novel molecular targets with potential therapeutic implications in lung cancer. In this review a comprehensive overview of standard oncogene-directed therapies of advanced NSCLC is provided, challenges in overcoming resistance to those therapies are discussed and novel oncogene-directed therapies under development are brieﬂy presented.