Isogenic human disease models are a family of cells that are selected or engineered to accurately model the genetics of a specific patient population, in vitro. They are provided with a genetically matched 'normal cell' to provide an isogenic system to research disease biology and novel therapeutic agents. They can be used to model any disease with a genetic foundation. Cancer is one such disease for which isogenic human disease models have been widely used. Historical models Human isogenic disease models have been likened to 'patients in a test-tube', since they incorporate the latest research into human genetic diseases and do so without the difficulties and limitations involved in using non-human models. Historically, cells obtained from animals, typically mice, have been used to model cancer-related pathways. However, there are obvious limitations inherent in using animals for modelling genetically determined diseases in humans. Despite a large proportion of genetic conservation between humans and mice, there are significant differences between the biology of mice and humans that are important to cancer research. For example, major differences in telomere regulation enable murine cells to bypass the requirement for telomerase upregulation, which is a rate-limiting step in human cancer formation. As another example, certain ligand-receptor interactions are incompatible between mice and humans. Additionally, experiments have demonstrated important and significant differences in the ability to transform cells, compared with cells of murine origin. For these reasons, it remains essential to develop models of cancer that employ human cells. Targeting vectors Isogenic cell lines are created via a process called homologous gene-targeting. Targeting vectors that utilize homologous recombination are the tools or techniques that are used to knock-in or knock-out the desired disease-causing mutation or SNP (single nucleotide polymorphism) to be studied. Although disease mutations can be harvested directly from cancer patients, these cells usually contain many background mutations in addition to the specific mutation of interest, and a matched normal cell line is typically not obtained. Subsequently, targeting vectors are used to 'knock-in' or 'knock out' gene mutations enabling a switch in both directions; from a normal to cancer genotype; or vice versa; in characterized human cancer cell lines such as HCT116 or Nalm6. There are several gene targeting technologies used to engineer the desired mutation, the most prevalent of which are briefly described, including key advantages and limitations, in the summary table below. Homologous recombination in cancer cell disease models Homologous recombination (HR) is