TY - JOUR

T1 - Cell Death of Tumor Melanocytes and Treatment Options

AU - Koval, Olga

AU - Zhilnikova, Maria

AU - Balantaeva, Maria

AU - Biryukov, Mikhail

AU - Atamanov, Vasiliy

N1 - This work was supported by the Russian Science Foundation, project no. 23-14-00285 (https:// www.rscf.ru) (accessed on 12 January 2025).

PY - 2025/3/31

Y1 - 2025/3/31

N2 - 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.

AB - 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.

KW - Cutaneous melanoma

KW - cell death

KW - cuproptosis

KW - ferroptosis

KW - gp100

KW - immune checkpoints inhibitors

KW - immunogenic cell death

KW - p53

KW - tyrosinase-related protein 1

KW - uveal melanoma

UR - https://www.mendeley.com/catalogue/499ec992-a91b-3d08-bd34-44001e27c9da/

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-105001876651&origin=inward&txGid=2172e6811cc5dc4553c5da546ceaee0d

U2 - 10.32604/biocell.2025.059987

DO - 10.32604/biocell.2025.059987

M3 - Article

VL - 49

SP - 355

EP - 379

JO - Biocell

JF - Biocell

SN - 1667-5746

IS - 3

ER -