Abstract 2462: AXL-WRNIP1 mediated replication stress response aids metastatic latency and relapse

Abstract Metachronous brain metastases, the primary cause of morbidity and mortality in HER2+ breast cancer patients arise from latent residual cells that resist systemic therapies. AXL, a receptor tyrosine kinase, is enriched in metachronous brain metastatic lesions from HER2+ breast cancer patients and in latent metastatic models. In contrast to its known function at the cell surface, AXL is localized to the nucleus and interacts with WRNIP1. Moreover, we show AXL depletion results in an increased replication stress and reduced survival of brain-tropic latent residual and metastatic cells. Furthermore, administration of BGB324 as a neoadjuvant sensitives brain metastatic lesions to targeted therapy. Our findings suggest targeting AXL is a viable option to eradicate residual brain metastatic cells and limit relapses in HER2+ breast cancer patients. Citation Format: Mauricio Marquez-Palencia, Srinivas Malladi. AXL-WRNIP1 mediated replication stress response aids metastatic latency and relapse [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2462.