Grant: Project Grant

Breast cancer is a common malignancy that affects 1 in 8 Canadian women in their lifetime. Despite progress in understanding the causes of breast cancer and its classification into defined subtypes, treatment of metastatic breast cancer still represents a highly unmet medical need. Specifically, patients with the basal-like subtype of breast cancer (BLBC) have a poor outcome owing to the clinically aggressive behavior of the disease and the lack of hormonal or targeted therapies. There is therefore an urgent need for the development of innovative therapeutic strategies to address the challenge of treating advanced metastatic BLBC. Our laboratory has recently unveiled a novel role of the protein kinase ERK3 in promoting the growth of BLBC. The objective of this proposal is to define the role of ERK3 kinase in BLBC progression and validate its therapeutic potential using preclinical BLBC models. The specific aims of the project are: (1) To evaluate the role of ERK3 signaling in BLBC metastasis and drug resistance in mouse models; (2) To investigate the role of ERK3 as a survival factor in hypoxic BLBC; and (3) To elucidate the molecular mechanisms underlying the pro-tumorigenic actions of ERK3 in BLBC progression. Our proposal has the potential to lead to the validation of a new therapeutic target in BLBC, which will spur the future development of chemical inhibitors of ERK3 for cancer therapy.