Marco Rubatto, Silvia Borriello, Nadia Sciamarrelli, Valentina Pala, Luca Tonella, Simone Ribero, Pietro Quaglino
{"title":"Exploring the role of epigenetic alterations and non-coding RNAs in melanoma pathogenesis and therapeutic strategies.","authors":"Marco Rubatto, Silvia Borriello, Nadia Sciamarrelli, Valentina Pala, Luca Tonella, Simone Ribero, Pietro Quaglino","doi":"10.1097/CMR.0000000000000926","DOIUrl":null,"url":null,"abstract":"Melanoma is a rare but highly lethal type of skin cancer whose incidence is increasing globally. Melanoma is characterized by high resistance to therapy and relapse. Despite significant advances in the treatment of metastatic melanoma, many patients experience progression due to resistance mechanisms. Epigenetic changes, including alterations in chromatin remodeling, DNA methylation, histone modifications, and non-coding RNA rearrangements, contribute to neoplastic transformation, metastasis, and drug resistance in melanoma. This review summarizes current research on epigenetic mechanisms in melanoma and their therapeutic potential. Specifically, we discuss the role of histone acetylation and methylation in gene expression regulation and melanoma pathobiology, as well as the promising results of HDAC inhibitors and DNMT inhibitors in clinical trials. We also examine the dysregulation of non-coding RNA, particularly miRNAs, and their potential as targets for melanoma therapy. Finally, we highlight the challenges of epigenetic therapies, such as the complexity of epigenetic mechanisms combined with immunotherapies and the need for combination therapies to overcome drug resistance. In conclusion, epigenetic changes may be reversible, and the use of combination therapy between traditional therapies and epigenetically targeted drugs could be a viable solution to reverse the increasing number of patients who develop treatment resistance or even prevent it. While several clinical trials are underway, the complexity of these mechanisms presents a significant challenge to the development of effective therapies. Further research is needed to fully understand the role of epigenetic mechanisms in melanoma and to develop more effective and targeted therapies.","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":null,"pages":null},"PeriodicalIF":1.5000,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Melanoma Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/CMR.0000000000000926","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/10/2 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"DERMATOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Melanoma is a rare but highly lethal type of skin cancer whose incidence is increasing globally. Melanoma is characterized by high resistance to therapy and relapse. Despite significant advances in the treatment of metastatic melanoma, many patients experience progression due to resistance mechanisms. Epigenetic changes, including alterations in chromatin remodeling, DNA methylation, histone modifications, and non-coding RNA rearrangements, contribute to neoplastic transformation, metastasis, and drug resistance in melanoma. This review summarizes current research on epigenetic mechanisms in melanoma and their therapeutic potential. Specifically, we discuss the role of histone acetylation and methylation in gene expression regulation and melanoma pathobiology, as well as the promising results of HDAC inhibitors and DNMT inhibitors in clinical trials. We also examine the dysregulation of non-coding RNA, particularly miRNAs, and their potential as targets for melanoma therapy. Finally, we highlight the challenges of epigenetic therapies, such as the complexity of epigenetic mechanisms combined with immunotherapies and the need for combination therapies to overcome drug resistance. In conclusion, epigenetic changes may be reversible, and the use of combination therapy between traditional therapies and epigenetically targeted drugs could be a viable solution to reverse the increasing number of patients who develop treatment resistance or even prevent it. While several clinical trials are underway, the complexity of these mechanisms presents a significant challenge to the development of effective therapies. Further research is needed to fully understand the role of epigenetic mechanisms in melanoma and to develop more effective and targeted therapies.
期刊介绍:
Melanoma Research is a well established international forum for the dissemination of new findings relating to melanoma. The aim of the Journal is to promote the level of informational exchange between those engaged in the field. Melanoma Research aims to encourage an informed and balanced view of experimental and clinical research and extend and stimulate communication and exchange of knowledge between investigators with differing areas of expertise. This will foster the development of translational research. The reporting of new clinical results and the effect and toxicity of new therapeutic agents and immunotherapy will be given emphasis by rapid publication of Short Communications. Thus, Melanoma Research seeks to present a coherent and up-to-date account of all aspects of investigations pertinent to melanoma. Consequently the scope of the Journal is broad, embracing the entire range of studies from fundamental and applied research in such subject areas as genetics, molecular biology, biochemistry, cell biology, photobiology, pathology, immunology, and advances in clinical oncology influencing the prevention, diagnosis and treatment of melanoma.