title: Retinoblastoma.
abstract: Retinoblastoma is a rare cancer of the infant retina that is diagnosed in approximately 8,000 children each year worldwide. It forms when both retinoblastoma gene (RB1) alleles are mutated in a susceptible retinal cell, probably a cone photoreceptor precursor. Loss of the tumour-suppressive functions of the retinoblastoma protein (pRB) leads to uncontrolled cell division and recurrent genomic changes during tumour progression. Although pRB is expressed in almost all tissues, cone precursors have biochemical and molecular features that may sensitize them to RB1 loss and enable tumorigenesis. Patient survival is >95% in high-income countries but <30% globally. However, outcomes are improving owing to increased disease awareness for earlier diagnosis, application of new guidelines and sharing of expertise. Intra-arterial and intravitreal chemotherapy have emerged as promising methods to salvage eyes that with conventional treatment might have been lost. Ongoing international collaborations will replace the multiple different classifications of eye involvement with standardized definitions to consistently assess the eligibility, efficacy and safety of treatment options. Life-long follow-up is warranted, as survivors of heritable retinoblastoma are at risk for developing second cancers. Defining the molecular consequences of RB1 loss in diverse tissues may open new avenues for treatment and prevention of retinoblastoma, as well as second cancers, in patients with germline RB1 mutations.
authors.affiliation: Department of Ophthalmology and Vision Sciences, The Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada.
authors.forename: Helen
authors.initials: H
authors.lastname: Dimaras
authors.affiliation: Eugene and Marilyn Glick Eye Institute, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Corson
authors.affiliation: The Vision Center, Children's Hospital Los Angeles &USC Eye Institute, University of Southern California, Los Angeles, California, USA.
authors.forename: David
authors.initials: D
authors.lastname: Cobrinik
authors.affiliation: World Eye Cancer Hope (previously Daisy's Eye Cancer Fund), Oxford, UK.
authors.forename: Abby
authors.initials: A
authors.lastname: White
authors.affiliation: Department of Ophthalmology, Beijing Children's Hospital, Capital Medial University, Beijing, China.
authors.forename: Junyang
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Ophthalmology, Jules-Gonin Eye Hospital, Lausanne, Switzerland.
authors.forename: Francis L
authors.initials: FL
authors.lastname: Munier
authors.affiliation: Department of Ophthalmology, Memorial Sloan Kettering Cancer Center, New York City, New York, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: Abramson
authors.affiliation: Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
authors.forename: Carol L
authors.initials: CL
authors.lastname: Shields
authors.affiliation: Hospital JP Garrahan, Buenos Aires, Argentina.
authors.forename: Guillermo L
authors.initials: GL
authors.lastname: Chantada
authors.affiliation: Department of Child Health and Paediatrics, Moi University, Eldoret, Kenya.
authors.forename: Festus
authors.initials: F
authors.lastname: Njuguna
authors.affiliation: Department of Ophthalmology and Vision Sciences, The Hospital for Sick Children and University of Toronto, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada.
authors.forename: Brenda L
authors.initials: BL
authors.lastname: Gallie
mesh_terms: D063646:Carcinogenesis / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D016161:Genes, Retinoblastoma / Q000235:genetics; D018095:Germ-Line Mutation; D006801:Humans; D007223:Infant; D016609:Neoplasms, Second Primary / Q000235:genetics; D019572:Retinal Neoplasms / Q000235:genetics*; D012175:Retinoblastoma / Q000235:genetics*; D016160:Retinoblastoma Protein / Q000235:genetics
chemical_list: D016160:Retinoblastoma Protein