title: Personalized Therapy of Small Cell Lung Cancer.
abstract: Small cell lung cancer (SCLC) is an aggressive, poorly differentiated neuroendocrine carcinoma with distinct clinical, pathological and molecular characteristics. Despite robust responses to initial chemotherapy and radiation, the prognosis of patients with SCLC remains poor with an overall 5-year survival rate of less than 10 %. Despite the fact that numerous molecularly targeted approaches have thus far failed to demonstrate clinical utility in SCLC, further advances will rely on better definition of the biological pathways that drive survival, proliferation and metastasis. Recent next-generation, molecular profiling studies have identified many new therapeutic targets in SCLC, as well as extreme genomic instability which explains the high degree of resistance. A wide variety of anti-angiogenic agents, growth factor inhibitors, pro-apoptotic agents, and epigenetic modulators have been evaluated in SCLC and many studies of these strategies are on-going. Perhaps the most promising approaches involve agents targeting cancer stem cell pathways and immunomodulatory drugs that interfere with the PD1 and CTLA-4 pathways. SCLC offers many barriers to the development of successful therapy, including limited tumor samples, inadequate preclinical models, high mutational burden, and aggressive tumor growth which impairs functional status and hampers enrollment on clinical trials.
authors.affiliation: Division of Hematology/Oncology, University of Michigan, C411 Med Inn-SPC 5848, 1500 E. Medical Center Dr., Ann Arbor, MI, 48109-5848, USA. bryansch@umich.edu.
authors.forename: Bryan J
authors.initials: BJ
authors.lastname: Schneider
authors.affiliation: Division of Hematology/Oncology, University of Michigan, C350 Med Inn-SPC 5848, 1500 E. Medical Center Dr., Ann Arbor, MI, 48109-5848, USA. kalemker@umich.edu.
authors.forename: Gregory P
authors.initials: GP
authors.lastname: Kalemkerian
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D042822:Genomic Instability; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000276:immunology; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D057285:Precision Medicine; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis
chemical_list: D000970:Antineoplastic Agents; D060908:CTLA-4 Antigen; D007155:Immunologic Factors; D009363:Neoplasm Proteins; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor
keywords: Genetic profiling; Immunotherapy; Lung cancer; Small cell; Targeted therapy