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

Cancers (Basel). 2023 Jul 12;15(14):3593. doi: 10.3390/cancers15143593.

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.

Keywords: conjunctival melanoma; eye cancer; ocular malignancies; p53 pathways; pterygium; retinoblastoma; therapy; tumor treatment; uveal melanoma.

Publication types

  • Review

Grants and funding

This manuscript was supported by local funds from the University of Ferrara, grant numbers: 2022-PRN-PR.A-SP_001, 2021-FAR.L-CF_002 and 2022-FAR.L-CF_004.