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This difference in the orders of magnitude poses assay-development challenges ranging from selecting an adequate sample volume for the assay to the optimization of reagent concentrations and sample-separation and -detection settings

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Functionally, each pathway circumvents melanomas intrinsic apoptosis resistance, and their dysregulationvia genetic mutations, epigenetic silencing, or metabolic reprogrammingcontributes to tumor progression and therapeutic resistance, highlighting their shared role as tumor-suppressive mechanisms when functionally intact (112, 114)

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