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tumor development and its clinical correlation in shaping future targeted treatment strategies |  |\n\nShruti Rathore, Aman Verma, Ria Ratna1, NavjotMarwa, Yagya Ghiya, Santosh G Honavar2, Anil Tiwari,  \nSima Das, Akhil Varshney  \nRetinoblastoma is a retinal cancer that affects children and is the most prevalent intraocular tumor worldwide. Despite tremendous breakthroughs in our understanding of the fundamental mechanisms that regulate progression of retinoblastoma, the development of targeted therapeutics for retinoblastomahas lagged. Our review highlights the current developments in the genetic, epigenetic, transcriptomic, and proteomic landscapes of retinoblastoma. We also discuss their clinical relevance and potential implications for future therapeutic development, with the aim to create a frontline multimodal therapy for retinoblastoma.  \nKey words: Biomarker, epigenetics, genomics, proteomics, retinoblastoma, targeted therapeutics, therapeutics, transcriptomics  \n\n| Access this article online |\n| --- |\n| Website:\u003Cbr>[https://journals.lww.com/ijo](https://journals.lww.com/ijo) |\n| DOI:\u003Cbr>10.4103/IJO. IJO_3172_22 |\n|  |\n| Quick Response Code:\u003Cbr>|\n\nRetinoblastoma is the most common pediatric eye cancer in children, accounting for about 2.5%–4% of all pediatric cancersin developed countries, with a relatively higher incidence rate of 4.4 per million in moderate to low–income countries in the ages between 1 and 4 years.[1] If left untreated, the condition is lethal, with a global survival rate of less than 30% .[2] The root cause of retinoblastoma is the biallelic inactivation of the RB1 gene, but additional genomic alterations such as genomic gain of 1q, 2p, and 6p, along with the genomic loss of 16q may also contribute to the progression of the tumor.[3]  \nAvailable therapeutic options to treat retinoblastoma include enucleation, cry otherapy, transpupillary thermotherapy, plaque brachytherapy, external beam radiotherapy, and systemic chemotherapy. Systemic chemotherapy involves the use of drugs such as carboplatin, cisplatin, vincristine, etoposide, topotecan, cyclophosphamide, and doxorubicin. [4] While the standard treatment of retinoblastoma has been effective in terms of tumor control, its non‑selective nature and associated systemic adverse effects pose a major challenge. Recently, super‑selective intra‑arterial chemotherapy has replaced systemic chemotherapy for the treatment of intraocular retinoblastoma; however, it has ocular and systemic side effects [Table 1] . [5] The management of retinoblastoma varies depending on the stage of the disease, the patient’sage at the time of presentation, the tumor’s location, size,  \nOcular Oncology Services, 1Ocular Genetics Services, Dr. Shroff’s Charity Eye Hospital, New Delhi, 2Ophthalmic Plastic Surgery, Orbit  \nand Ocular Oncology, Centre for Sight, Hyderbad, Telangana, India Correspondence to: Dr. Sima Das, Ocular Oncology Services, Dr. Shroff’s Charity Eye Hospital, Daryaganj New Delhi, India.  \nE‑mail: [contactsima@gmail.com](contactsima@gmail.com)  \nReceived: 04‑Dec‑2022  \nAccepted: 21‑May‑2023  \nRevision: 25‑Apr‑2023  \nPublished: 05‑Jul‑2023  \nand laterality, societal perception, and cost‑effectiveness of the treatment. [6] While these methods have proven to be effective for most patients, they have several limitations, including side effects such as partial or complete vision loss, immune response–generated inflammation, dry eye disease, retinal detachment, focal iris atrophy, focal lens opacity, retinal traction, and late ocular and systemic side effects, such as bone marrow suppression, autotoxicity, nephrotoxicity, and high chances of developing cataract, ptosis, and secondary malignancies after treatment. [7] As a result of non‑targeted drug deliveries, these therapies can lead to severe complexities that can cause on‑target off‑tumor toxicity. [8]  \nTherefore, a pa","cbCaijpkIB7sehS0","https://ap.wps.com/l/cbCaijpkIB7sehS0","pdf",5197987,15,"English","# Introduction\n# Molecular basis of retinoblastoma\n# Current therapeutic options and limitations\n# Toward targeted treatment strategies","[{\"question\":\"What genetic event is considered the root cause of retinoblastoma?\",\"answer\":\"Retinoblastoma is rooted in biallelic inactivation of the RB1 gene, with additional genomic alterations that also contribute to progression.\"},{\"question\":\"Which omics areas does the review highlight for retinoblastoma research?\",\"answer\":\"The review highlights genetic, epigenetic, transcriptomic, and proteomic landscapes to capture the tumor’s molecular drivers.\"},{\"question\":\"Why is a move toward targeted therapies needed?\",\"answer\":\"Conventional therapies are often non-selective and can cause significant systemic and ocular side effects, so targeted approaches are proposed to improve anti-tumor response with fewer complications.\"}]","Retinoblastoma: A review of the molecular basis of tumor development and its clinical correlation in shaping future targeted treatment strategies | PDF",1790563476,38]