The National Cancer Institute estimates there are over 280,000 new cases of invasive breast cancer in the U.S. alone each year. In invasive estrogen receptor (ER)-positive breast cancers (representing approximately 60% of cases), patients are currently treated with endocrine therapy, which impacts estrogen’s effects in cancer cells, and CDK 4/6 inhibitors. However, because the majority of patients eventually progress, there is an immense need for new treatments.
Breast cancers often harbor overexpressed or mutated RTKS such as HER2 or FGFR, that can be treated with either approved or experimental agents that specifically target those proteins. In preclinical experiments, we have shown that zotatifin downregulates production of proteins within the ER and RTK pathways. We are advancing our product candidate zotatifin in several breast cancer subtypes, including ER+, Her2+ and FGFR+ metastatic breast cancer both as a single agent as well as in combination with targeted agents.
We are also evaluating tomivosertib in combination with taxane in patients with metastatic breast cancer. This trial, led by McGill University and fully funded through a grant from Stand Up To Cancer (SU2C) Canada, will further our understanding of the MNK pathway and chemotherapy-induced stress response.