Targeted Drug Discovery
Personalised medicines are fast being realized to hold significant cost and performance advantages over conventional drugs that do not target the root causes of a disease; such as the genetic mutations that lead to the onset of human cancer.
However, there is currently a lack of accurate laboratory-based models that perfectly recapitulate the various human cancer genotypes to enable the routine and efficient discovery of drugs that target these specific mutations.
Current Disease Models
Non-isogenic cell models that have been isolated over many years from individual cancer patients differ genetically in hundreds of ways, making it difficult to understand a drugs true mechanism. Many secondary assays are therefore required to build confidence in drug’s mode-of-action and utility.
Other available methods that enable the ‘artificial’ study of a specific disease-associated gene only ever approximate the real disease situation and often, in a manifestly different context to that seen in humans:
- RNAi, only partially removes a target gene’s activity; which in many cases will be insufficient to yield an effect on a cell. In addition, RNAi is neither a stable nor specific mechanism.
- Ectopic gene expression systems fail to mimic the complex regulation and feedback loops that exist in the proper genomic context
These models, while high-throughput in nature, can easily lead to misleading findings on the role of putative cancer genes and drugs that target them.