Single-cell RNA sequencing in melanoma: what have we learned so far?

Malignant Melanoma: An Overview, New Perspectives, and Vitamin D Signaling

“…Malignant transformation of melanocytes and further progression to advanced stages of melanoma are driven by environmentally induced somatic mutations in a cellular, tissue, and systemic context-dependent fashion as discussed in numerous reviews [ 1 , 2 , 4 , 6 , 10 , 11 , 18 , 30 , 36 , 37 , 74 , 76 , 77 , 82 , 86 , 126 , 127 , 128 , 129 , 130 ]. Therefore, our overview on this topic will be brief.…”

“…The pathological and clinical staging allows precise prediction of the natural history of the disease, including overall survival (OS) and disease-free survival (DF) times, and when supplemented by ancillary studies (IHC) or molecular testing (GP, GEP, NEGS) form a basis for an educated selection of appropriate therapeutic approaches. It must be noted that the staging of melanoma would likely be modified and/or supplemented by deposited RNA sequencing data, proteomic data, or metabolomic data at publicly available databases with implications for future therapy [ 1 , 11 , 18 , 30 , 48 , 74 , 75 , 76 , 77 , 79 , 127 , 130 , 134 , 159 , 165 , 169 , 175 , 176 , 177 , 178 , 179 , 180 , 181 , 182 , 183 ]. This will be further discussed in Section 5.5 : Bioinformatics Considerations of Melanoma Diagnosis and Treatment.…”

“…The developing resistance to targeted- or immuno-therapy leading to recurrent disease and death of the patient represents a significant challenge. There are different mechanisms underlying this negative phenomenon, including tumor heterogeneity with pre-existing mutations allowing clonal expansion of resistant cells, mutations during therapy and progression of the disease, mutator phenotype, metabolic heterogeneity, and dynamic changes in the tumor microenvironment, to name a few [ 4 , 6 , 25 , 30 , 37 , 74 , 75 , 87 , 130 , 165 , 178 , 179 , 182 , 211 , 218 , 229 , 230 , 231 , 232 , 233 ]. It must be noted that melanoma itself can affect the host response at local and systemic levels through production of neurohormonal regulators (as expected because of the neural crest origin of melanocytes) with immunosuppressive properties [ 3 , 50 , 82 , 234 ], including intermediates of melanogenesis and melanin that would increase resistance to any type of therapy [ 4 , 235 , 236 ].…”

Angiogenesis Still Plays a Crucial Role in Human Melanoma Progression

“…Regarding the therapeutic ways, ITH is a critical determinant of treatment response and resistance, leading to the selection and outgrowth of drug-resistant cancer cells, and some papers have demonstrated that increased ITH is associated with resistance to targeted therapies and immunotherapies, affecting treatment outcomes [124]. Challenges remain in the widespread adoption of scRNA-seq due to cost, technical complexity, and data analysis requirements, so future research should focus on leveraging scRNA-seq to dissect the heterogeneity of melanoma cell states, identify therapeutic targets, and overcome treatment resistance.…”