State of the Art of Pharmacological Activators of p53 in Ocular Malignancies

SIMPLE SUMMARY: Ocular malignancies encompass a broad range of disorders that affect the eyelids, orbit, and eye and have significant impacts for national healthcare systems. Due to its exposure to various stressors, the eye is an anatomical site susceptible to cellular toxicity and tissue damage, which can result in significant vision loss. In this context, similar to other tissue types, p53 plays a crucial role in maintaining ocular homeostasis. However, few in vitro experimentation and clinical trials of p53 pathway modulators have been conducted. The aim of this review is to discuss the potential of pharmacological p53 activators as a novel targeted therapy for managing ocular tumors. ABSTRACT: The pivotal role of p53 in the regulation of a vast array of cellular functions has been the subject of extensive research. The biological activity of p53 is not strictly limited to cell cycle arrest but also includes the regulation of homeostasis, DNA repair, apoptosis, and senescence. Thus, mutations in the p53 gene with loss of function represent one of the major mechanisms for cancer development. As expected, due to its key role, p53 is expressed throughout the human body including the eye. Specifically, altered p53 signaling pathways have been implicated in the development of conjunctival and corneal tumors, retinoblastoma, uveal melanoma, and intraocular melanoma. As non-selective cancer chemotherapies as well as ionizing radiation can be associated with either poor efficacy or dose-limiting toxicities in the eye, reconstitution of the p53 signaling pathway currently represents an attractive target for cancer therapy. The present review discusses the role of p53 in the pathogenesis of these ocular tumors and outlines the various pharmacological activators of p53 that are currently under investigation for the treatment of ocular malignancies.