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

• Type of Material: Article
• 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
• Language: English
• Date: 2016-04-01
• Publisher: Lippincott, Williams & Wilkins
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc.
• Final Published Version (URL): http://dx.doi.org/10.1016/j.jtho.2016.01.012
• Title of Journal or Parent Work: Journal of Thoracic Oncology
• ISSN: 1556-0864
• Volume: 11
• Issue: 4
• Start Page: 453
• End Page: 474
• Keywords: Oncology; DOUBLE-BLIND; COMPREHENSIVE GENOMIC ANALYSIS; Life Sciences & Biomedicine; PHASE-II-TRIAL; THERAPEUTIC TARGET; Respiratory System; Small cell lung cancer; AURORA KINASE; Immunotherapy; Gene mutations; Science & Technology; NEUROENDOCRINE CARCINOMAS; MOUSE MODEL; CIRCULATING TUMOR-CELLS; Therapy; SOLID TUMORS; STEM-CELLS; Neuroendocrine
• Research Categories: Biology, Molecular; Health Sciences, Rehabilitation and Therapy; Health Sciences, Oncology

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.