Malignant melanoma is a type of very dangerous skin cancer.,Histone modifiers usually become dysregulated during the process of carcinoma development, thus there is potential for a histone modifier inhibitor as a useful drug for cancer therapy.,There is a multitude of evidence regarding the role of G9a, a histone methyltransferase (HMTase), in tumorigenesis.,In this study, we first showed that G9a was significantly upregulated in melanoma patients.,Using the TCGA database, we found a significantly higher expression of G9a in primary melanoma samples (n = 461) compared to normal skin samples (n = 551).,Next, we knocked down G9a in human M14 and A375 melanoma cell lines in vitro via small interfering RNA (siRNA).,This resulted in a significant decrease in cell viability, migration and invasion, and an increase in cell apoptosis.,UNC0642 is a small molecule inhibitor of G9a that demonstrates minimal cell toxicity and good in vivo pharmacokinetic characteristics.,We investigated the role of UNC0642 in melanoma cells, and detected its anti-cancer effects in vitro and in vivo.,Next, we treated cells with UNC0642, and observed a significant decrease in cell viability in M14 and A375 cell lines.,Furthermore, treatment with UNC0642 resulted in increased apoptosis.,In immunocompetent mice bearing A375 engrafts, treatment with UNC0642 inhibited tumor growth.,Results of Western blot analysis revealed that administration of UNC0642 or silencing of G9a expression by siRNA reduced Notch1 expression significantly and decreased the level of Hes1 in A375.,All in all, the data from our study demonstrates potential of G9a as a therapeutic target in the treatment of melanoma.
Melanoma is the deadliest form of skin cancer.,In the early stages, melanoma can be treated successfully with surgery alone and survival rates are high, but after metastasis survival rates drop significantly.,Therefore, early and correct diagnosis is key for ensuring patients have the best possible prognosis.,Melanoma misdiagnosis accounts for more pathology and dermatology malpractice claims than any cancer other than breast cancer, as an early misdiagnosis can significantly reduce a patient’s chances of survival.,As far as treatment for metastatic melanoma goes, there have been several new drugs developed over the last 10 years that have greatly improved the prognosis of patients with metastatic melanoma, however, a majority of patients do not show a lasting response to these treatments.,Thus, new biomarkers and drug targets are needed to improve the accuracy of melanoma diagnosis and treatment.,This article will discuss the major advancements of melanoma diagnosis and treatment from antiquity to the present day.