Targeting DNA damage repair in small cell lung cancer and the biomarker landscape

With an estimated 250,000 cases worldwide annually, small cell lung cancer (SCLC) is the sixth major cause of cancer-related mortality (1-7). SCLC is the most aggressive form of lung cancer, characterized by rapid tumor growth and early metastatic spread (8,9). Currently, chemotherapy remains the cornerstone of treatment for both limited stage (LS) and extensive stage (ES)-SCLC, with a majority of patients obtaining an objective response with first-line treatment, as described by Farago and Keane (current standards for clinical management of SCLC) also in this issue. However, despite high rates of response initially, the duration of clinical response is extremely limited in most cases and almost all patients relapse—often within a few months (5,6,8,9). Recently, clinical trials have demonstrated that some SCLC patients can obtain durable responses to immunotherapy and this has led to the addition of nivolumab with or without ipilimumab to the NCCN treatment guidelines as the first non-chemotherapy option for relapsed SCLC (10,11). However, beyond this there are currently no targeted agents for the treatment of SCLC approved by the United States Food and Drug Administration (FDA)