Transcriptional dysregulation and insights into clinical implications in melanoma

Melanoma, a highly prevalent cancer worldwide, exhibits remarkable diversity and plasticity, with the adverse prognosis of advanced melanoma remaining a focal point of investigation. Despite the emergence of novel drugs and combination therapies improving patient outcomes, challenges such as drug resistance and incomplete mechanistic understanding persist. Transcriptional programs play a pivotal role in determining the characteristics of both normal and tumour cells, with their dysregulation of these programs being a hallmark of melanoma. Abnormalities in transcription regulation not only impact the characteristics of melanoma cells but also influence the tumor’s metabolism and immune microenvironment, forming a complex network in tumours. Thus, understanding these changes comprehensively is crucial for unravelling the mechanisms underlying melanoma initiation, progression, response to targeted and immune therapies, and treatment resistance. This review primarily explores the transcriptional features in normal melanocytes and melanoma cells, emphasizing their profound impact on cell metabolism and immune evasion. Furthermore, the plasticity of melanoma cells and its relationship with treatment resistance and metastasis are highlighted, emphasizing the importance of targeting dysregulated transcriptional factors and pathways. Finally, potential clinical implications in targeting transcriptional abnormalities are highlighted, particularly in metastatic or treatment-resistant melanomas. This comprehensive overview aims to contribute to the advancement of melanoma research and the development of precise and effective treatments.