Treatment of RB‐deficient retinoblastoma with Aurora‐A kinase inhibitor

Abstract

Abstract Retinoblastoma, also known as ocular cancer, usually affects children under the age of five. The standard of care for managing early‐stage retinoblastoma is a combination of vincristine, carboplatin, and etoposide. However, this combination‐based modality has limited applications owing to its side and late effects. Moreover, in advanced tumor stages, nearly 50% of patients would suffer a partial or full loss of vision. Therefore, therapies that preserve vision and reduce side effects are urgently required. Here, we focused mainly on the common loss‐of‐function (LOF) mutation of retinoblastoma gene 1 (RB1) in advanced retinoblastoma and investigated the synthetic lethality between RB1‐LOF and Aurora kinase inhibition. We showed that Aurora kinase A inhibition could lead to cell mitotic abnormality and apoptosis, and demonstrated in vivo efficacy in a mouse model xenografted with RB1‐deficient retinoblastoma. Our findings provide a promising druggable molecular target and potential clinical strategy for tackling retinoblastoma disease.

Keywords

• Aurora kinase a (AURKA)
• retinoblastoma
• retinoblastoma gene 1 (RB1)
• synthetic lethality