**3. Current biomarkers in melanoma**

According to the National Institutes of Health Biomarkers Definitions Working Group, biomarkers, or "biological markers," are "a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention" [14]. Biomarkers are commonly used in both clinical trials and clinical practice because of its multitude of applications: as diagnostics for identifying patient conditions or diseases, as a tool for staging and characterization of disease, as an indicator of disease progression, or as a predictor of treatment response [14].

Tumor markers are specifically biomarkers of cancer. They are usually proteins that are tumor-derived (produced by the tumor cells) or tumor-associated (produced by the body in response to tumor cells development) [15]. Tumor markers can appear in a variety of samples, but the most commonly used specimens for detection are blood serum and urine. Both are viable for these purposes because of the ease of collection and processing, as well as the secretion of distinctive cancer markers into these fluids.

Proteins are the most common tumor marker because of their central roles in cell signaling and influence on key molecular pathways in various cells and systems of the body. They are often most easily measurable through immunohistochemistry as certain protein levels change between normal and tumor cells. However, many other molecules can also serve as tumor markers. Cell-free circulating tumor DNA (ctDNA) were characterized in the late 1980s and since then, it has been found that ctDNA is correlated with tumor size and disease activity [16, 17]. ctDNA can be analyzed through liquid biopsies and PCR-based assays [18]. Circulating tumor cells (CTCs) are often present in advanced neoplasias that have metastatic potential and can be purified from serum on the basis of different cell surface markers compared to normal blood cells [18, 19]. Serum metabolites are small molecules secreted by tumor cells that can often serve as a signature of the tumor [20–22]. Carbohydrate expression also changes during oncogenic transformation and cancer progression and can serve as a measure of cancer stage [23–25].

This chapter will specifically examine RNA as biomarkers. In recent years, differing transcriptomes among tumor and healthy cells have become a point of emphasis. Several cancers have different noncoding RNA expression profiles in a time- and tissue-dependent manner. Changes in miRNA within a specific tissue has been shown to correlate with disease status including tumor invasiveness and metastatic potential in various cancers such as breast, colorectal, hepatic, lung, pancreatic, and prostate [26]. LncRNAs can also be used as serum tumor markers, which we will examine in detail in the following section.
