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REVIEW

Cell Death of Tumor Melanocytes and Treatment Options

Olga Koval1,2,*, Maria Zhilnikova1, Maria Balantaeva1,2, Mikhail Biryukov1,2, Vasiliy Atamanov1,3
1 Department of Biotechnology, Institute of Chemical Biology and Fundamental Medicine SB RAS, Novosibirsk, 630090, Russia
2 Department of Natural Sciences, Novosibirsk State University, Novosibirsk, 630090, Russia
3 Department of Reconstructive Surgery, The S. Fedorov Eye Microsurgery Federal State Institution, Novosibirsk, 630120, Russia
* Corresponding Author: Olga Koval. Email: email
(This article belongs to the Special Issue: Cell Death and Inflammation in Signaling and Diseases)

BIOCELL https://doi.org/10.32604/biocell.2025.059987

Received 21 October 2024; Accepted 13 January 2025; Published online 12 February 2025

Abstract

Melanomas are aggressive cancers, with a high rate of metastatic disease. Cutaneous (CM) and uveal (UM) melanomas are intrinsically different diseases, and most cell death inducers effective for CM do not function for UM. This is primarily due to the fact the eye is an immunologically privileged organ, and it fails to achieve the efficacy of immune checkpoint inhibitors (ICIs) comparable to that for CM. However, approaches utilizing specific melanoma-associated antigens are being developed for metastatic forms of CM and UM. The most promising to date are gp100 and tyrosinase related protein 1 (TYRP1), primarily for the design of targeting chimeric molecules and for autologous T-/NK-cell products with a chimeric antigen receptor. The difference in the mutational profile of apoptosis-related genes in CM and UM also makes counterproductive the use of the same drugs re-activators of the intrinsic pathway of apoptosis. Therefore, the discovery of novel pathways of regulated cell death such as ferroptosis and cuproptosis may help in the development of new drugs for melanomas resistant to already available inducers of regulated cell death. Here we consistently discuss the latest advances in the therapy of melanomas, and above all-UM, which is classified as an orphan disease.

Keywords

Cutaneous melanoma; uveal melanoma; cell death; p53; ferroptosis; cuproptosis; immune checkpoints inhibitors; immunogenic cell death; tyrosinase-related protein 1; gp100

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