Pharmacological inhibitors to prevent rogue spliceosome functioning in breast cancer

Pharmacological inhibitors are small molecules that bind to specific biomolecules and prevent them from performing their biological functions. They are useful tools towards the development of new therapeutics, and for developing our understanding of biochemical pathways. Our project aims to prepare selective inhibitors for biomolecules (CLKs) involved in the ‘spliceosome’, a complex molecular machine found in all human cells that enables correct formation of proteins. Proteins perform almost all the important cellular functions in our bodies. When the spliceosome malfunctions, mutant proteins are generated that promote cancer development and progression. Therapeutic targeting of the spliceosome by selective CLK inhibition may prevent rogue functioning, and in the longer term will be key in developing molecular tools that can deconvolute its roles in cancer. The CLKs are implicated to play roles in a range of cancers, notably including breast cancer – the most common cause of cancer for New Zealand women. Every day, breast cancer takes the lives of two New Zealand women. Māori women have one of the highest incidences of breast cancer worldwide – 60% higher than Pākehā. Further, the Canterbury region has a notably higher number of cancer registrations than the national average. Increasing our understanding of breast cancer development and progression at the molecular level is paramount to discovering the next generation of effective personalised treatments.