ATYR2810

Interestingly, the chemokine receptor CXCR4, which is known to promote drug resistance and tumorigenic potential, was found to be significantly downregulated in responder PDX tumors treated with ATYR2810 in combination with cisplatin as compared to those treated with cisplatin alone. Taken together, our data suggest that ATYR2810 enhances chemosensitivity in highly aggressive TNBC subtypes, and that this response may be mediated through the downregulation of genes known to be associated with aggressive cancer states such as ZEB1 and CXCR4. ATYR2810 may therefore serve as a novel therapeutic agent for the treatment of advanced and metastatic TNBC and potentially other aggressive cancer types.Zhiwen Xu and Alison Barber are co-first authors of this abstract.

We have shown that ATYR2810, but not a Sema3F-blocking mAb has tumor-inhibitory effects on triple negative breast cancer (TNBC) cell lines or patient-derived organoids. We further evaluated the efficacy of ATYR2810 in combination with standard-of-care therapeutics including Cisplatin and Bevacizumab (anti-VEGF-A blocking antibody). These results demonstrate the efficacy of ATYR2810 in combination with standard-of-care therapeutics in in vitro and in vivo TNBC models, and suggest its activity is mediated through inhibiting both EMT and cellular dedifferentiation that renders tumors more sensitive to the treatment regimes. The targeting of VEGF/NRP2 signaling by ATYR2810 may provide a new therapeutic option, and lead to the identification of new treatment biomarkers, which could offer improved efficacy and reduced toxicity in aggressive breast cancers.