Small Cell Lung Cancer: Can Recent Advances in Biology and Molecular Biology Be Translated into Improved Outcomes?

• Authors: Paul A. Bunn, University of Colorado; John Minna, University of Texas Southwestern Medical Center; Alexander Augustyn, University of Texas Southwestern Medical Center; Adi Gazdar, University of Texas Southwestern Medical Center; Youcef Ouadah, Stanford University; Mark A. Krasnow, Stanford University; Anton Berns, Netherlands Cancer Institute; Elisabeth Brambilla, Grenoble University; Natasha Rekhtman, Memorial Sloan Kettering Cancer Center; Pierre P. Massion, Vanderbilt University; Taofeek Owonikoko, Emory University
• Journal Title: Journal of Thoracic Oncology
• Volume: Volume 11, Number 4
• Publisher: Lippincott, Williams & Wilkins | 2016-04-01, Pages 453-474
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1016/j.jtho.2016.01.012
• Subjects: Health Sciences, Oncology; Biology, Molecular; Health Sciences, Rehabilitation and Therapy
• Keywords: Science & Technology; Life Sciences & Biomedicine; Oncology; Respiratory System; Small cell lung cancer; Gene mutations; Therapy; Immunotherapy; Neuroendocrine; PHASE-II-TRIAL; COMPREHENSIVE GENOMIC ANALYSIS; CIRCULATING TUMOR-CELLS; SOLID TUMORS; DOUBLE-BLIND; STEM-CELLS; NEUROENDOCRINE CARCINOMAS; THERAPEUTIC TARGET; AURORA KINASE; MOUSE MODEL

Abstract

Small cell lung cancer (SCLC) is one of the four major histologic types of lung cancer. The incidence of SCLC in developed countries has declined in recent years, presumably due to changes in cigarette composition. In the United States (US) SCLC is estimated to represent about 16% of new lung cancer diagnoses, which equates to about 35,000 new cases annually. In underdeveloped countries the percentage of SCLC cases may be higher. SCLC presents with a very large number of genetic alterations, including tumor suppressor genes, copy number gains and other somatic mutation in transcription factors, enzymes involved in chromatin modification, receptor tyrosine kinases and their downstream signaling components 1. SCLC has a high propensity for early spread and a high initial responsiveness to cytotoxic chemotherapy usually followed by rapid development of resistance. Thus, essentially all patients of any stage receive a doublet combination of etoposide with cisplatin or carboplatin. For the rare patient without nodal involvement, the chemotherapy may follow surgery and for the patient with nodal disease without distant metastases, a combination of chemotherapy with chest radiotherapy is usually given concurrently. Unfortunately, these therapies are short in duration and not curative in most instances with 5-year survival rates below 7%. No major treatment advances have occurred over the past 30 years2. Since the approval of topotecan in 1996, the US Food and Drug Administration (FDA) has not approved any new drugs for the treatment of SCLC patients 3. For these reasons SCLC was declared a “recalcitrant” cancer in the US. However, considerable therapeutic opportunities, including targeted therapies, exist because of recent developments in understanding the biology and molecular biology of SCLC in part due to the new model systems.