residual tumor cells that drive disease relapse after chemotherapy do not have enhanced tumor initiating capacity残余肿瘤细胞驱动疾病复发肿瘤化疗后没有增强启动能力.pdfVIP

Residual Tumor Cells That Drive Disease Relapse after Chemotherapy Do Not Have Enhanced Tumor Initiating Capacity 1 1 2 3 Ganapati V. Hegde , Cecile de la Cruz , Jeffrey Eastham-Anderson , Yanyan Zheng , E. Alejandro Sweet- 3 1 Cordero , Erica L. Jackson * 1 Department of Discovery Oncology, Genentech, Inc., South San Francisco, California, United States of America, 2 Department of Pathology, Genentech, Inc., South San Francisco, California, United States of America, 3 Cancer Biology Program, Department of Pediatrics, Stanford University School of Medicine, Stanford, California, United States of America Abstract Although chemotherapy is used to treat most advanced solid tumors, recurrent disease is still the major cause of cancer- related mortality. Cancer stem cells (CSCs) have been the focus of intense research in recent years because they provide a possible explanation for disease relapse. However, the precise role of CSCs in recurrent disease remains poorly understood and surprisingly little attention has been focused on studying the cells responsible for re-initiating tumor growth within the original host after chemotherapy treatment. We utilized both xenograft and genetically engineered mouse models of non- small cell lung cancer (NSCLC) to characterize the residual tumor cells that survive chemotherapy treatment and go on to cause tumor regrowth, which we refer to as tumor re-initiating cells (TRICs). We set out to determine whether TRICs display characteristics of CSCs, and whether assays used to define CSCs also provide an accurate readout of a cell’s ability to cause tumor recurrence. We did not find consistent enrichment of CSC marker positive cells or enhanced tumor initiating potential in TRICs. However, TRICs