The Role of Transcriptional and Atypical Cyclin-Dependent Protein Kinases in Melanoma

Melanoma, a skin cancer with the highest mortality rate, poses a significant medical challenge. Despite the revolution in the treatment of this cancer brought about by the development of immunotherapy and targeted therapies using BRAF/MEK inhibitors, the complex mutation profile and the development of drug resistance compel researchers to seek new solutions. Cyclin-dependent kinases (CDKs), a group of enzymes regulating fundamental processes in every eukaryotic cell, are generating significant interest in the context of potential targeted therapies for melanoma. The best-studied CDKs, responsible for controlling specific phases of the cell-cycle, have been extensively described in the literature, and their inhibition is increasingly used as a treatment for various cancers. However, in addition to the classic cell-cycle CDKs, CDKs regulating transcription can also be distinguished. Other family members responsible for tissue-specific processes are commonly referred to as atypical or untypical CDKs. These include CDK5, which plays a critical role in the nervous system. In recent years, a growing body of research has focused on the role of transcriptional and atypical CDKs in the progression of cancers, including melanoma. However, their precise function remains unclear. This paper will provide an overview of the role of CDKs, other than cell cycle CDKs, in melanoma development and provide a comprehensive understanding of their potential use in future targeted therapies. The advantages and disadvantages of inhibiting these kinases in melanoma therapy will be discussed, as well as the synergies with various molecular pathways analyzed to date.