Heterogeneity of Small Cell Lung Cancer Stem Cells
Small cell lung cancer, a subtype of lung cancer is an extremely malignant disease due to its metastases and recurrence. Patients with SCLC develop resistance to chemotherapy and the disease relapses. This relapse and resistance are attributed to the hete
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Heterogeneity of Small Cell Lung Cancer Stem Cells D. Prabavathy and Niveditha Ramadoss
Abstract Small cell lung cancer, a subtype of lung cancer is an extremely malignant disease due to its metastases and recurrence. Patients with SCLC develop resistance to chemotherapy and the disease relapses. This relapse and resistance are attributed to the heterogeneity of SCLC. Various factors such as recurrent mutations in key regulatory genes such as TP53, RB1, and myc, epigenetic changes, and cancer stem cells contribute to the observed heterogeneity. Cancer stem cell models predict neuroendocrine origin of SCLC. Though an unambiguous established CSC marker has not been assigned, markers CD133, CD44 have been found associated with SCLC. Genetically engineered mouse models (GEMMs) allow the validation of driver mutations and are necessary for design of targeted therapy. This chapter outlines the factors contributing to SCLC heterogeneity, detection methods, and the current therapy trials. Keywords SCLC · Neuroendocrine markers · CD133 · CD44 · Side population cells · Intratumor heterogeneity · TP53 · RB1 · Clonal evolution · CSC model · Lysine demethylase 1 · Notch pathway · Genetically engineered mouse model
3.1 Introduction Globally lung cancer accounts for more than one-tenth of all cancer cases and is one of the most common types of cancer. The major risk factor for the development of lung cancer is smoking. Due to smoking the lung cells are exposed to carcinogens which induce extensive mutations. Mutations that accumulate in different oncogenes and tumor suppressors lead to tumor genesis in lung cancers. A range of morphological appearances and genetic aberrations observed in lung cancers
D. Prabavathy (*) Department of Biotechnology, School of Bio and Chemical Engineering, Sathyabama Institute of Science and Technology, Chennai, Tamil Nadu, India N. Ramadoss Department of Biology, California State University Northridge, Northridge, CA, USA © Springer Nature Switzerland AG 2019 A. Birbrair (ed.), Stem Cells Heterogeneity in Cancer, Advances in Experimental Medicine and Biology 1139, https://doi.org/10.1007/978-3-030-14366-4_3
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D. Prabavathy and N. Ramadoss
indicate heterogeneity of the disease. Lung cancer is broadly classified into non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). The most abundant form of lung cancer is NSCLC and comprises several subclasses that include adenocarcinomas, squamous cell carcinomas, and large cell carcinomas. SCLC represents about 15% of all lung cancer cases and can be distinguished by its neuroendocrine (NE) features (Govindan et al. 2006). SCLC shows the most rapid growth and metastasizes to distant sites of the body (Jackman and Johnson 2005). Small cell lung cancer (SCLC) is an extremely aggressive cancer that cytotoxic chemotherapies fail to exterminate. It affects >200,000 people world-wide every year with a very high mortality rate. Combination chemotherapy with cisplatin, hyperfractionated thoracic radiation, and prophylactic cranial irra
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