Abstract 3856: Identification of circulating tumour cells in breast cancer patient-derived xenograft models

Abstract

Abstract Metastases from primary tumours accounts for the great majority of cancer-related deaths. This process is thought to involve a series of sequential steps, with the release of circulating tumour cells (CTCs) into the blood stream. CTCs have been detected in the peripheral blood of patients with advanced cancers of different origin and in some localized cancers. Recently, liquid biopsy focusing on the analysis of CTCs has received enormous attention because of its obvious clinical implications for personalized medicine. Clinical applications of CTCs detection include early detection of cancer, prediction of the risk for metastatic relapse or progression, monitoring the effects of systemic therapies, and stratification of patients based on the detection of therapeutic targets on resistance mechanisms. To date, only few data are available about the numbers of these cells, their molecular and biological heterogeneity, and their significance. CTCs comprise a minute fraction of mononucleated cells in the circulation, posing a serious challenge for any analytical system. Multiple technologies have been developed for CTC capture, but there is still a critical need for increased sensitivity in rare tumour cell isolation within blood specimens. Most of the current CTC detection techniques rely on antibody-based capture of cells, and epithelial markers have been frequently used to distinguish cancer cells from normal blood cells. However, the phenotypic changes that occur in CTCs, due predominantly to the epithelial-mesenchymal transition process, could be responsible for the failure to detect them in blood samples. We describe a novel approach for the identification of molecular markers to detect CTCs in peripheral blood of patient-derived xenograft (PDX) models. We analyzed the transcriptome in more than 10,000 samples of primary and metastatic tumours deposited in public databases, and identified a small set of cancer-specific genes coding for membrane protein. Putative markers were assayed by reverse transcription PCR with species-specific primers in blood samples from breast cancer PDXs, testing their ability to detect human CTCs. Thus, we identified human membrane proteins, which can be used for CTC monitoring in peripheral blood. The use of multiple targets for CTC capture and identification increases the sensitivity of CTC detection, allowing the isolation of all heterogeneous CTCs subpopulations. Citation Format: Chiara Agnoletto, Linda Minotti, Marco Galasso, Fabio Corrà, Federica Baldassari, Stefano Cairo, Jean-Gabriel Judde, Aurelie Sauvage, Olivier Deas, Lorenzo Pasquali, Stefano Volinia. Identification of circulating tumour cells in breast cancer patient-derived xenograft models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3856. doi:10.1158/1538-7445.AM2017-3856