eFFECTOR Therapeutics in collaboration with investigators at Baylor College of Medicine announced the presentation of new positive data for zotatifin in animal models of triple-negative breast cancer (TNBC) at the 2021 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics. Zotatifin is a potent and sequence-selective inhibitor of eukaryotic translation initiation factor 4A (eIF4A) mediated translation. The study authors found that blocking eIF4A in p53-null models of mouse mammary tumorigenesis with zotatifin results in tumor control via both tumor-intrinsic mechanisms as well as activation of host immune response. This activity is further potentiated with the addition of chemotherapy. In the study, zotatifin treatment slowed tumor growth in six out of eight syngeneic TNBC models without apparent toxicity. Zotatifin treatment was also shown to inhibit proliferative and stem cell signaling pathways including E2F targets, G2/M checkpoints, as well as NOTCH signaling, and induce proteins involved in Interferon-a and Interferon-y responses. Additionally, combination treatment of zotatifin with the mTOR inhibitor everolimus demonstrated statistically significant prolonged survival compared to use of these agents alone.