Horizon is a part of this fight, providing in vitro and in vivo disease models to advance research, services to drive drug development programs, and reference standards so that assays used in development or to diagnose patients are as accurate as possible.
Select a bar in the table to update this content
Horizon is a leading provider of genetically defined, human genomic reference standards, including Formalin-Fixed Paraffin-Embedded (FFPE) cell line sections and purified genomic DNA (gDNA). HDx™ Reference Standards offer a sustainable source of reference material to laboratories, proficiency schemes and manufacturers, providing an unprecedented level of control.
Drawing upon our proprietary genome editing platform, we engineer clinically relevant cancer genes in human cell lines, exactly as they occur in patient tumors. In this way we are able to define virtually every characteristic of our reference standards, from the molecular constitution of the genome to DNA output associated with each product batch.
We offer several Reference Standards for breast cancer related biomarkers, primarily for Fluorescence In Situ Hybridization (FISH) material and Immunohistochemistry (IHC) assays.
We also develop custom reference standards to meet your needs.
An unparalleled resource for the characterization of genes and their role in disease biology and drug response, X-MAN® Cell Lines can be used to study the role of any gene in a variety of cellular processes and thus provides a tractable model for the study of human gene function. Parental lines, used as optimal controls, include a selection of common cell lines as well as the proprietary haploid cell line (HAP1), providing unique tools for hypothesis testing. Furthermore, the validated guide RNAs used to produce gene-edited HAP1 cell lines are available to extend your findings to your particular in-house cell line model.
Horizon offers off the shelf and on demand knockout or knockin cell lines for a wide range of breast-cancer linked genes:
The same team of cell line engineering scientists who developed our extensive cell line catalog are also available to generate cell lines on your behalf. Using our genome-editing platform, which comprises CRISPR, rAAV, and ZFN technologies, we are able to make almost any genetic alteration required, from simple knockouts or single point mutations to more complex genomic manipulations.
If you can't find the breast cancer cell line you need for your experiment in our catalog, Horizon's highly experienced scientists can provide a custom tailored service.
Horizon is your source for unique, next-generation SAGE® animal research models featuring specific gene deletions, insertions, repressions and modifications, as well as the industry's first and only knockout rat model.
Tumor heterogeneity is a challenge in cancer research and drug development. While cancer cell lines are enormously valuable for in vitro sensitivity and combination studies, they do not offer a comprehensive view of the tumor microenvironment. For this reason patient-derived xenograft (PDX) tumor models have been increasingly leveraged to generate predictive efficacy data to help inform clinical trial design. The Horizon PDX models are implanted as dissociated cell suspensions into immunodeficient mice which allows for highly reproducibly-sized tumors with which to evaluate oncology drug candidates. . Investigators may explore the effect of their oncology drug candidate, using our PDX efficacy study service, or using frozen dissociated cells to initiate these studies in their own facilities.
Features of Horizon’s PDX Breast Cancer model collection include:
Horizon provides in vitro assay development and drug screening services powered by our precision gene-editing, human isogenic cell line platforms and disease microenvironment assays.
Our scientists are experts in the development and application of cell-based assays. In addition to standard cell survival and proliferation assays, we can carry out co-culture assays to model the tumor microenvironment, analyze the effects of hypoxia through the use of spheroid assays or low oxygen incubators, grow cells in soft agar for medium throughput assessment of viability and proliferation, and examine senescence and autophagy induction.
In particular, we have two breast cell lines that have been optimised for anchorage-independent soft agar assays (MCF7 and MDA-MB-231)
Horizon has coupled our isogenic cell line library with our understanding of cancer biology and the tumor microenvironment along with a broad selection of libraries to be able to offer a range of screening approaches and assay conditions suitable to meet the requirements of almost any project.
Horizon has established a core expertise in functional genomic screens using gene trap, siRNA and CRISPR-Cas9 screening platforms. These techniques can be used to find and validate novel drug targets, to identify mechanisms of drug resistance or sensitivity and to identify synthetic lethal targets.
Screening approaches well suited for breast cancer research. For example, BRCA2 -/- cell lines are ideal for evaluating the effects of PARP inhibitors. We have also optimised MCF10A mammary epithelial cell line for CRISPR-Cas9 screening experiments.
Combination therapies are now emerging as the standard of care in indications such as cancer, inflammation, diabetes, and infectious disease. Horizon’s Combination High Throughput Screening platform (cHTS) operates by comparing a drug or other compound with a second at a specific dose to look for synergistic or antagonistic effects. These are seen by either increasing the anti-proliferative or cell killing effect.
How can Horizon’s combination drug screening platform work for you?
Horizon has extensive experience performing combination studies in the field of breast cancer:
Looking for a knockout rat or mouse not included in our standard model portfolio? Your Horizon in vivo model development specialist will work with you to design a custom model to your exact specifications, using our CRISPR-Cas9 or Zinc Finger Nuclease technologies, in as few as 5 months.
If you can't find the breast cancer in vivo model you need for your experiment in our catalog, Horizon's highly experienced scientists can provide a custom tailored service.
Almost every disease has some degree of genetic influence, however in cancer genetic alterations can have a huge impact on disease onset and progression. This is complicated by the fact that cancer is not a single uniform disease, but instead is caused by the presence of multiple genetic mutations that can vary in number and composition between patients. Moreover, the genetics of cancer often vary between individual cells within the same tumor and its metastases, making diagnosis and therapeutic decisions more difficult.
As a result, genetic biomarkers are increasingly important when determining the patient populations who are likely to respond to a therapeutic during the drug discovery and development process, and to identify those patients who should receive the drug upon diagnosis. Unsurprisingly, tremendous efforts are underway to determine which mutations in which genes are important disease drivers or predictive markers of drug responsiveness or resistance.
Horizon was founded to help identify and make use of these genetic biomarkers for oncology. We translate genomic information into practical drug discovery and diagnostic tools that accurately recreate the specific genetics of real patients that are significant in human cancer onset and progression.
Horizon’s gene editing platform confers the ability to rapidly introduce any genetic variation, including subtle, yet highly significant ‘gain-of-function’ disease mutations (common in many forms of cancer), into any endogenous gene loci of any human cell line; thus accurately modeling real patient genotypes.
These disease models take the form of cell lines, which are being used widely in basic and drug discovery research and provide them as tools, use them as the basis of a wide range of services to power drug discovery and development programs, and offer them as reference standards to help ensure that patient diagnostic testing provides accurate results. Our gene editing platform also is used to generate in vivo models to support drug trials, particularly in the preclinical stage.
Gustin, J.P., et al. Knock in of mutant PI3CA activates multiple oncogenic pathways, PNAS 2009;106(8):2835-2840.
Grassian et al. IDH1 Mutations Alter Citric Acid Cycle Metabolism and Increase dependence on Oxidative Mitochondrial Metabolism, Cancer Res 2014;74:3317-3331
Kapp JR, Diss T, Spicer J, et al. Variation in pre-PCR processing of FFPE samples leads to discrepancies in BRAF and EGFR mutation detection: a diagnostic RING trial, J Clin Pathol 2015;68:111–118.
Patton S. et al. Assessing standardization of molecular testing for non-small-cell lung cancer: results of a worldwide external quality assessment (EQA) scheme for EGFR mutation testing, British Journal of Cancer 2014;111, 413–420
Alexandra R. Grassian et al. (2012). Isocitrate Dehydrogenase (IDH) Mutations Promote a Reversible ZEB1/MicroRNA (miR)-200-dependent Epithelial-Mesenchymal Transition (EMT), THE JOURNAL OF BIOLOGICAL CHEMISTRY VOL. 287, NO. 50, pp. 42180–41294
Richard J. Rickles et al. (2012). Adenosine A2A and Beta-2 Adrenergic Receptor Agonists: Novel Selective and Synergistic Multiple Myeloma Targets Discovered through Systematic Combination Screening, Mol Cancer Ther; 1–11., 2012