Retinoblastoma: Molecular Classification and Stratification

Retinoblastoma is a rare pediatric malignant tumor of the developing retina, with well-known genetic etiology caused in most cases by bi-allelic inactivation of the RB1 gene. In hereditary cases, often affecting both eyes, a germline RB1 alteration is present. Future challenges to improve retinoblastoma understanding and identify new therapeutic targets rely on cutting-edge molecular approaches to identify of retinoblastoma subtypes with distinct prognosis. The steps ahead include to define the molecular categories, to determine a level of aggressiveness for each category, to merge the molecular risk factors with the current clinical and histopathological classifications, and finally to adapt the treatment to each category. Advances are currently limited by the obtention of tumor material only in advanced cases requiring enucleation, sometimes after initial attempt of conservative treatment using chemotherapy that may modify histopathological and molecular findings. This limit may be soon overcome by the advent of “liquid biopsy” by analyzing cell-free tumor DNA from the aqueous humor before treatment. Molecular-based risk stratification will hopefully improve therapeutic strategies in the management of retinoblastoma.