Novel treatments’ approaches in retinoblastomacancer: Focusing on drug delivery, drug repurposing,and immunotherapy

Retinoblastoma (Rb) is the most common intraocular malignancywith high priority from World Health Organization (WHO)among pediatric cancers. Although chemotherapy and focaltherapy approaches still serve as a cornerstone of Rb patients'treatment, more optimal targeted novel approaches should beconsidered to minimize the chemotherapy side effects, resolvingchallenges such as distant metastasis to the central nervoussystem and lymph nodes, risk of secondary malignancy, poorprognosis, etc. In this review, we first examined the genetic andepigenetic role in Rb's pathophysiology and personalized medicine’scontribution to its diagnosis. In the next step, in-vitro andin-vivo studies, clinical trials, and also insilico studies on threenovel approaches (drug delivery, drug repurposing, and immunotherapy)for Rb are thoroughly discussed by searching Pub-Med, Google Scholar, Clinicaltrails.gov, and other databases.Existing chemotherapy approaches include systematic chemotherapybased on VEC protocol, intra-arterial and intra-vitrealchemotherapy. The more specific and insightful strategy isdesigning novel biomaterial-based drug delivery for chemotherapeuticagents to skip obstacles. Moreover, paradigm advancesin cancer therapy have appertained to immunotherapyapproaches which are more common in breast and liver cancerbut also seem a promising strategy for future treatment of Rb.These approaches include genetically modified cells, chimericT cell receptor (CAR T cell) therapy, gene therapy, and potentialtargeted therapy (such as immune checkpoint inhibitors,anti-gangliosides, antibodies, and small molecules for inhibitingdifferent targets in the pathways of Rb’s pathophysiology)which can be beneficial not even on tumor cells but also fortargeting the tumor microenvironment (TME) and protein communication.In addition, drug repurposing is a cost-benefit approachin most cancers. However, unlike other cancers, limitedtrials and even high-throughput screening are available for Rb.Altogether, these novel approaches may turn the obstacles inthe future management of Rb by reducing existing challenges.

کلیدواژه ها:

Retinoblastoma ، Immunotherapy ، Repurposing ، Intra-vitreal ، chemotherapy