National Cancer Institute Research Funding for melanoma reached $132.8 million in 2015 . Most of our current knowledge about melanoma comes from the research of patients from the United States and European populations. registered in the USA (1487), which is 58% of the total. The Paullinic acid most commonly studied drug in clinical trials was ipilimumab, described as applied intervention in 251 trials. (4) An increase in the number of melanoma clinical trials using immunomodulating monoclonal antibody therapies, small molecule-targeted therapies (inhibitors of BRAF, MEK, CDK4/6), and combination therapies is recognized. This illustrates the tendency towards precision medicine. gene and less frequently due to mutations in and genes [21,22,23]. The two most well characterized mutations commonly found in melanomas are (~40%) and (~20%) [14,22]. These mutations also occur with high frequencies in benign mutation alone is not sufficient to drive malignant transformation of melanocytes. Driver mutations that promote melanoma progression include: the TElomerase Reverse-Transcriptase ((gain of invasive potential), Phosphatase-and-TEnsin homologue (and its small GTPase substrate, ((associated with melanocyte proliferation), and neurofibromin 1 (gene, most common in mucosal melanomas derived from the genital regions or mutations in G Protein Subunit Alpha 11 (mutant melanomas (~50% of melanomas), (ii) (mutant melanomas (~15% of melanomas), and (iv) prone pathway, which is initiated by early sun exposure and promoted by an intermittent sun exposure or possible host factors, characterized by young age at diagnosis and absence of chronic sun damage on the skin, and concerns mainly melanomas on the trunk and superficial spreading melanomas; and (ii) a chronic sun exposure pathway in sun sensitive people who progressively accumulate sun exposure to the sites of future melanomasthis pathway is characterized by mutations without any associations with count  (Figure 2). Open in a separate window Figure 2 Differential dependence of melanoma subgroups on sun exposure and types of gene mutations. The interplay of genetic and environmental factors on melanoma development. Up to 50% of melanomas derived from the skin without chronic sun damage (intermittently exposed to UV) Paullinic acid contain mutations. The second frequent Paullinic acid mutations are present in the gene (around 25%). In melanomas derived from chronic sun exposure, and mutations are more common (~15% and ~20%) than (~10%). According to Janina Staub (2012) with some modifications [30,31]. 2. Methodology of Data Search In total, 2563 clinical trials registered in the ICTRP database were analyzed . ICTRP contains data from the largest authorities registering clinical tests. The database is constantly updated and includes data from Australian New Zealand Clinical Trials Registry, Chinese Clinical Trial Registry, ClinicalTrials.gov, EU Clinical Trials Register (EU-CTR), International Standard Randomised Controlled Trial Number Registry (ISRCTN), The Netherlands National Trial Register, Brazilian Clinical Trials Registry (ReBec), Clinical Trials RegistryIndia, Clinical Research Information ServiceRepublic of Korea, Cuban Public Registry of Clinical Trials, German Clinical Trials Register, Iranian Registry of Clinical Trials, Japan Primary Paullinic acid Registries Network, Pan African Clinical Trial Registry, Sri Lanka Clinical Trials Registry, Thai Clinical Trials Registry (TCTR), and Peruvian Clinical Trials Registry (REPEC). The search was performed on 30 November 2018 using the term melanoma. Trials in which melanoma was mentioned as a condition the test referred to were included in analysis without time or geographical restrictions. Historical Paullinic acid information about clinical trial outcomes and details was obtained from PubMed , FDA , World Health Organization (WHO) , American Cancer Society (ACS) , National Cancer Institute (NCI) , United States Cancer Statistics (USCS) , CDC, ECIS , and Cancer Australia . The dataset obtained was analyzed with the use of a proprietary script written in Python. The results obtained for the most common interventions were used to create the bubble chart. For each intervention, unique occurrences were counted, e.g., if a drug appeared in one clinical trial several times, for example, in combinations with different drugs, it MGP was counted as one occurrence. The obtained results reflect the number of unique clinical tests in which the medicine was given as the intervention used. This approach allowed us to avoid duplicates. 3. Historical Melanoma Clinical Trials BreakthroughsFDA Approval Overview The first clinical trial on melanoma registered in ICTRP started in 1971.