Signal pathways of melanoma and targeted therapy

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Abstract

Melanoma is the most lethal skin cancer that originates from the malignant transformation of melanocytes. Although melanoma has long been regarded as a cancerous malignancy with few therapeutic options, increased biological understanding and unprecedented innovations in therapies targeting mutated driver genes and immune checkpoints have substantially improved the prognosis of patients. However, the low response rate and inevitable occurrence of resistance to currently available targeted therapies have posed the obstacle in the path of melanoma management to obtain further amelioration. Therefore, it is necessary to understand the mechanisms underlying melanoma pathogenesis more comprehensively, which might lead to more substantial progress in therapeutic approaches and expand clinical options for melanoma therapy. In this review, we firstly make a brief introduction to melanoma epidemiology, clinical subtypes, risk factors, and current therapies. Then, the signal pathways orchestrating melanoma pathogenesis, including genetic mutations, key transcriptional regulators, epigenetic dysregulations, metabolic reprogramming, crucial metastasis-related signals, tumor-promoting inflammatory pathways, and pro-angiogenic factors, have been systemically reviewed and discussed. Subsequently, we outline current progresses in therapies targeting mutated driver genes and immune checkpoints, as well as the mechanisms underlying the treatment resistance. Finally, the prospects and challenges in the development of melanoma therapy, especially immunotherapy and related ongoing clinical trials, are summarized and discussed.

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Author and article information

Contributors

Chunying Li:

ORCID: http://orcid.org/0000-0003-3004-5376

lichying@fmmu.edu.cn

Journal

Journal ID (nlm-ta): Signal Transduct Target Ther

Journal ID (iso-abbrev): Signal Transduct Target Ther

Title: Signal Transduction and Targeted Therapy

Publisher: Nature Publishing Group UK (London )

ISSN (Print): 2095-9907

ISSN (Electronic): 2059-3635

Publication date (Electronic): 20 December 2021

Publication date PMC-release: 20 December 2021

Publication date Collection: 2021

Volume: 6

Electronic Location Identifier: 424

Affiliations

GRID grid.233520.5, ISNI 0000 0004 1761 4404, Department of Dermatology, Xijing Hospital, , Fourth Military Medical University, ; No. 127 of West Changle Road, 710032 Xi’an, Shaanxi China

Author information

Chunying Li http://orcid.org/0000-0003-3004-5376

Article

Publisher ID: 827

DOI: 10.1038/s41392-021-00827-6

PMC ID: 8685279

PubMed ID: 34924562

SO-VID: 0d4fca59-5def-48d2-8dbf-17246b57d899

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

History

Funding

Funded by: National Natural Science Foundation of China (No. 81625020)

Funded by: National Natural Science Foundation of China (No. 81902791) Support Program of Young Talents in Shaanxi Province (No.20200303) Young Eagle Project of Fourth Military Medical University (No.2019cyjhgwn)