Genomic Instability as a Therapeutic Target in Breast and Colorectal Cancer

Genetic information is contained in units of DNA in a cell called chromosomes. Normal cells rely upon checkpoints to control the passage of genetic information contained in chromosomes to daughter cells. The mitotic checkpoint, regulates the passage of genetic information before the formation of daughter cells and if this fails, cancers become resistant to death induced by the taxane breast cancer drug and develop resistance to other cancer drugs in the laboratory. Failure of the same checkpoint promotes gain or loss of whole chromosomes (called chromosomal instability, CIN cancers) associated with worse prognosis in cancer patients. Many patients with breast cancer experience side effects but derive limited or no benefit from taxane treatment. A CR-UK team will analyse breast cancer tissue from patients treated with taxanes within clinical trials to assess whether CIN is associated with taxane resistance. This may identify which patients may benefit from this treatment in the future. The CRUK team will identify how to selectively target CIN cancers to promote new approaches for anticancer drug discovery. These drugs may eventually limit the evolution of tumour drug resistance and have greater cancer-specificity, reducing side effects to normal tissue (skin, hair and white blood cells) with normal chromosome number.