Kristin Brown lab

TNBC is a subtype of breast cancer for which treatment options are largely limited to conventional chemotherapy agents. Chemotherapy resistance is a major barrier to the treatment of TNBC and there is a critical need to identify novel therapeutic strategies to treat this disease. We have previously shown that chemotherapy agents reprogram de novo pyrimidine synthesis and demonstrated that a clinically approved inhibitor of this metabolic pathway can sensitize TNBC cells to chemotherapy. We are continuing to investigate metabolic reprogramming events induced by chemotherapy and the contribution of the identified pathways to therapy resistance and tumour progression. 

Cancer cells employ diverse strategies to avoid elimination by the immune system. One of the primary mechanisms involves loss of immune recognition as a result of dysfunctions in antigen processing and presentation. Compromised antigen presentation has been observed across diverse tumour types and is associated with poor prognosis. In addition to impairing the ability of the immune system to control cancer, this mechanism of immune evasion negatively impacts the efficacy of clinically relevant immunotherapies. We are examining the metabolic dependencies of antigen processing and presentation with a view to identifying novel strategies to recover immune surveillance in cancer.

To meet the demands associated with rapid proliferation, cancer cells must be able to synthesise critical nutrients or acquire them from the surrounding microenvironment. Until recently, little attention has been paid to the fact that cell culture media does not mimic the in vivo metabolic environment. We have therefore adopted the use of a physiologically relevant media that can be manipulated to investigate the impact of nutrient availability on cancer cells. Coupled with genetic approaches to perturb metabolic pathway activity, we seek to identify the nutrient dependencies of cancer cells with a view to developing novel strategies for cancer therapy.