title: Modeling Breast Cancer Intertumor and Intratumor Heterogeneity Using Xenografts.
abstract: Breast cancer is a heterogeneous disease that can be stratified in at least 10 different subtypes. We present here a platform for derivation of preclinical models based on patient-derived tumor xenografts (PDTXs) that represent these subgroups. These models preserve the transcriptome, methylome, copy-number, and mutational landscape features of the tumor of origin through different passaging. Furthermore, the intratumoral composition of these models is formed by communities of clones very similar to the ones present in the originating tumor. Finally, we show that short-term cultures of cells from these models (PDTX-derived tumor cells, PDTCs) also preserve the molecular features of the tumor and can be used for high-throughput drug testing of single compounds or combinations, with high reproducibility and clinical predictive power.
authors.affiliation: Department of Oncology and Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge CB2 0RE, United Kingdom.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Bruna
authors.affiliation: Department of Oncology and Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge CB2 0RE, United Kingdom.
authors.forename: Oscar M
authors.initials: OM
authors.lastname: Rueda
authors.affiliation: Department of Oncology and Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge CB2 0RE, United Kingdom.|Breast Cancer Programme, Cambridge Cancer Centre, Cambridge CB2 2QQ, United Kingdom.
authors.forename: Carlos
authors.initials: C
authors.lastname: Caldas
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002965:Classification / Q000379:methods; D004195:Disease Models, Animal; D064593:Heterografts; D006801:Humans; D015203:Reproducibility of Results; D014183:Transplantation, Heterologous / Q000379:methods