Project description:Breast cancer is the most commonly diagnosed cancer among women. PDXs (patient-derived xenografts) are similar to cancer cell lines but differ in that they are maintained in a physiological setting as soon as they are isolated from the patient and for subsequent passages. These models are valuable for preclinical trials because PDX models have been shown to closely match their patient counterparts, both in genomic profile and response to treatment. One challenge to treatment development is tumor heterogeneity. In this study, we profiled ER+ and triple negative breast cancer PDX models using single-cell RNA-sequencing. This data may help identify populations of cells which are susceptible to certain treatments in order to improve clinical outcomes for breast cancer patients.
Project description:Breast cancer is the most commonly diagnosed cancer among women. PDXs (patient-derived xenografts) are similar to cancer cell lines but differ in that they are maintained in a physiological setting as soon as they are isolated from the patient and for subsequent passages. These models are valuable for preclinical trials because PDX models have been shown to closely match their patient counterparts, both in genomic profile and response to treatment. One challenge to treatment development is tumor heterogeneity. In this study, we profiled ER+ and triple negative breast cancer PDX models using single-cell RNA-sequencing. This data may help identify populations of cells which are susceptible to certain treatments in order to improve clinical outcomes for breast cancer patients.
Project description:The patient-derived xenograft (PDX) model retains the heterogeneity of patient tumors, allowing a means to not only examine efficacy of a therapy across a population, but also study crucial aspects of cancer biology in response to treatment. Herein we describe the development and characterization of an ovarian-PDX model in order to study the development of chemoresistance. We demonstrate that PDX tumors are not simply composed of tumor-initiating cells, but recapitulate the original tumor’s heterogeneity, oncogene expression profiles, and clinical response to chemotherapy. Combined carboplatin/paclitaxel treatment of PDX tumors enriches the cancer stem cell populations, but persistent tumors are not entirely composed of these populations. RNA-Seq analysis of treated PDX tumors compared to untreated tumors demonstrates a consistently contrasting genetic profile after therapy, suggesting similar, but few, pathways are mediating chemoresistance. The pathways most significantly altered included Protein Kinase A signaling, GNRH signaling, and sphingosine-1-phosphate signaling. Pathways and genes identified by this methodology represent novel approaches to targeting the chemoresistant population in ovarian cancer 6 pairs of Patient-Derived Xenografts (PDX) were ananlyzed using RNA-seq for a total of 12 samples. Each pair consists of a treated and untreated PDX of ovarian cancer. Treated Ovarian cancer PDXs were treated with 4 weeks of a combination of carboplatin and taxol. RNA was isolated and converted to cDNA. RNA-seq was conductred on the Illumina HiSeq 2000 with 50 bp paired end sequencing
Project description:Primary outcome(s): The detection rates of epigenetic heterogeneity in primary tumor and plasma from colorectal cancer patients with Methylation-sensitive high resolution melt(MS-HRM).