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

Kaohsiung J Med Sci. 2022 Mar;38(3):244-252. doi: 10.1002/kjm2.12469. Epub 2021 Nov 6.


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.

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Apoptosis
  • Aurora Kinase A / antagonists & inhibitors*
  • Cell Line, Tumor
  • Disease Models, Animal
  • Female
  • Genes, Retinoblastoma / genetics
  • Humans
  • Loss of Function Mutation
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Mitosis
  • Retinal Neoplasms / drug therapy*
  • Retinal Neoplasms / genetics
  • Retinal Neoplasms / pathology
  • Retinoblastoma / drug therapy*
  • Retinoblastoma / genetics
  • Retinoblastoma / pathology


  • Antineoplastic Agents
  • AURKA protein, human
  • Aurora Kinase A