<p>Retinoblastoma (Rb) represents a primary pediatric cancer, which if left untreated can invade to the nervous system that primarily occurs due to loss of the RB1 gene. Several clinically available therapies are used for the management of risk factors associated with Rb including chemotherapy, brachytherapy, external beam radiotherapy etc. However, each treatment has its own side effects. To meet with the best approach in order to minimize these side effects, novel targeted therapies have been developed that inhibit tumor in an angiogenic-dependent manner. This review provides the insights about some targets and the pharmaceuticals with their possible mechanism of action that targets angiogenesis and induces apoptosis. The targets include activation of p53 via controlling mouse double minute homolog 2, survivin, and thrombospondin-1. Entities described in this review include 5-aminoimidazole-4-carboxamide ribonucleotide, niclosamide, bevacizumab, aflibercept, genistein and quercetin and their potential in treating Rb. Also, the signaling pathways that are affected in response to these drugs like activated protein kinase pathway, Wnt/β-catenin pathway, vascular endothelial growth factor and its receptors has also been discussed.</p>
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