Predictive biomarkers of drug resistance and sensitivity in triple-negative breast cancer

Summary

Triple-negative breast cancer (TNBC) is the most aggressive form of breast cancer, accounting for 15% of all breast cancer cases in the UK. TNBC tends to happen in women below 50 and those of Afro-Caribbean ancestry, and we have a large group of these patients in Bristol. Our treatment for most TNBC patients is chemotherapy. Currently, doctors cannot predict which patients would or would not respond to chemotherapy. There are also limited treatment options for those who do not respond to chemotherapy. Thus, identifying patients who would not respond to chemotherapy but who might benefit from another treatment option is an important goal, as it can improve patient outcome and decrease healthcare cost.

From a clinical trial, we recently discovered that tumours of TNBC patients who did not respond to chemotherapy contain high levels of a particular protein called RASAL2. Surprisingly, the same protein also makes the tumours more sensitive to a specific class of drugs that are already in clinical use for other cancers. We propose to explore these findings by identifying proteins related to RASAL2 that could predict a patient's likelihood to respond to treatment (i.e. predictive biomarkers). This study will support future research that will aim to confirm the clinical value of these biomarkers. We expect our work to benefit TNBC patients who may not respond to standard chemotherapy and who might benefit from other treatment options.