Molecular Biology and Genetic Mechanisms in the Progression of the Malignant Skin Melanoma

Prilozi Pub Date : 2016-11-01 DOI:10.1515/prilozi-2016-0021
S. Pejkova, G. Dzokic, S. Tudzarova-Gjorgova, S. Panov
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引用次数: 7

Abstract

Abstract Malignant skin melanoma is a tumor deriving from transformed skin melanocytes as a result of complex interactions between genetic and environmental factors. This melanoma has a potential to metastasize early and very often it is resistant to the existing modalities of the systemic therapy. As in any other neoplasms, certain types of melanoma may skip certain stages of progression. The progression from one stage to another is accompanied by specific biological changes. Several key changes in the melanoma tumorogenesis influence the regulation of the cell proliferation and vitality, including the RAS-RAF-ERK, PI3K-AKT, and p16INK4/CDK4/RB pathways. A key role in the dissreguarity of the RAS-RAF-ERK (MAPK) pathway in the malignant melanoma development have been demonstrated by many studies. To date, the molecular genetic alterations during melanoma development have been partially known. In the pathogenesis of the malignant melanoma, there are mutations of various genes such as NRAS, BRAF, and PTEN and mutations and deletions of CDKN2A. In the past years, great advance has been made in the insights of the molecular aspects of the melanoma pathogenesis. However, this field yet poses a challenge to discover new details about the melanoma molecular characteristics. The research results are focused towards the improvement of the melanoma patients prognosis by introducing personalized targeted therapy.
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恶性皮肤黑色素瘤进展的分子生物学和遗传机制
恶性皮肤黑色素瘤是遗传和环境因素复杂相互作用的结果,是由皮肤黑色素细胞转化而来的肿瘤。这种黑色素瘤有早期转移的潜力,而且通常对现有的全身治疗方式有抗药性。和其他肿瘤一样,某些类型的黑色素瘤可能会跳过某些发展阶段。从一个阶段到另一个阶段的进展伴随着特定的生物学变化。黑色素瘤发生过程中的几个关键变化影响细胞增殖和活力的调节,包括RAS-RAF-ERK、PI3K-AKT和p16INK4/CDK4/RB通路。许多研究已经证明RAS-RAF-ERK (MAPK)通路的不稳定性在恶性黑色素瘤的发展中起关键作用。到目前为止,在黑色素瘤的发展过程中,分子基因的改变已经被部分了解。在恶性黑色素瘤的发病过程中,存在NRAS、BRAF、PTEN等多种基因的突变以及CDKN2A的突变和缺失。在过去的几年里,在黑色素瘤发病机制的分子方面的见解取得了很大的进展。然而,这一领域仍面临着发现黑色素瘤分子特征新细节的挑战。研究成果旨在通过引入个性化靶向治疗来改善黑色素瘤患者的预后。
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