Circulating tumor cells and CDX models as a tool for preclinical drug development.

Abstract

Lung cancers are the main cause of cancer-related deaths worldwide. Efforts placed to improve the survival of lung cancer patients and untangle the complexity of this disease, have resulted in the generation of hundreds of lung cancer cell lines and several genetically engineered mouse models (GEMMs). Although these research tools have extended our knowledge of lung cancer, improvement in the clinical care of lung cancer patients have been limited overall, with measured optimism regarding initial responses to targeted therapies in stratified subgroups of patients. Patient-derived xenograft (PDX) models are beginning to assist 'personalized therapy' approaches particularly in non-small cell lung cancer (NSCLC) however biopsies of lung cancers to generate PDXs are not without challenges and risks to the patient. Liquid biopsies, on the other hand, are a rapid and non-invasive procedure allowing the collection of circulating tumor cells (CTCs) with a single 10 mL blood draw. These CTCs recapitulate the molecular heterogeneity of the corresponding tumors and, therefore, can be used as surrogates to study tumor biology and generate new patient-derived models. Here, we discuss the CTC-derived models that have been generated, most notably in small cell lung cancer (SCLC), highlighting challenges and opportunities related to these novel preclinical tools.