Many of the deadliest cancers share a common feature: extreme Chromosomal Instability (CIN). CIN manifests as an accumulation of structural and numerical chromosomal abnormalities in cancer cells. These changes result in chaotic genomes, and are associated with metastasis, poor prognosis and treatment resistance.
Precision medicine approaches have improved the survival rates of many cancers. However, these improvements have been focussed on cancers without CIN. Cancers with extreme CIN have not seen significant improvements in overall survival. Therefore, there is an unmet need for treating cancers with extreme CIN.
Many precision medicine approaches are currently based on the detection of small single gene mutations. However, the chaotic genomic landscape caused by CIN limits our ability to personalise treatment using single gene mutations as a target.
Instead, we use CIN signatures, which are patterns of change of chromosomal copy numbers, to personalise treatment. Different types of CIN leave unique genomic footprints that can be linked to specific mutational processes. These processes are often the same across multiple different tumour types. Hence, we can use these signatures as pan-cancer biomarkers for targeting defective pathways.
A deeper understanding of the underlying mechanisms of CIN enables new opportunities in precision medicine.
Tailor Bio’s technology platform unlocks new methods of drug target discovery for the development of pan-cancer precision therapies. Additionally, it enables us to stratify patients according to their treatment response to different targeted therapies and chemotherapy.
Macintyre et al., Nature Genetics, August 2018
Drews et al., Nature, June 2022