**2. The importance of early diagnosis**

Melanoma is diagnosed as an AJCC stage I, II, III, or IV. Stages I and II are characterized as melanomas of varying Breslow thicknesses and possible ulceration, but with no lymph node involvement or metastases. Depending on the sub-stage, 5-year survival ranges from 53% to a robust 97% [4]. Stage III is characterized by regional metastases with 5-year survival rates of 40–78% depending on sub-stage [4]. Stage IV is characterized by distant metastases with extremely poor prognosis and 1-year survival rates ranging from 33 to 62% depending on location of metastases and serum LDH level [4].

There have been recent breakthroughs in melanoma treatments for stages IIIC and IV. Common therapies approved by the Food and Drug Administration include both immunotherapy and small molecule targeted therapy. Both immunotherapy drugs such as pembrolizumab (anti-PD-1) [5, 6], nivolumab (anti-PD-1) [7], and ipilimumab (anti-CTLA-4) [7, 8], and small molecules inhibitors such as dabrafenib (BRAF inhibitor) [9], vemurafenib (BRAF inhibitor) [10], and trametinib (MEK inhibitor) [11] have improved patient survival. However, most tumors become drug-resistant shortly after commencing therapy, resulting in disease progression [12, 13]. Unfortunately, our current therapies are more of a temporary stay than a permanent cure.

Thus, the best way to ensure long-term survival is to diagnose the malignancy while it is in its early stages and slow disease progression through surgery and adjuvant therapy. Melanoma biomarkers play an important role in the diagnosis and prediction of the progression of the disease. However, they have severe limitations in regard to precision to detect early stages of melanoma and reliability as a predictor of disease prognosis and treatment response. By understanding the molecular basis of the disease more, we can identify novel biomarkers that can be used to more efficiently diagnose disease which will undoubtedly improve outcomes and quality of life.
