Department of Pediatrics and Pharmacology, Pennsylvania State University College of Medicine, Hershey, PA-17033, USA.
Biochemistry Department, College of Science and Technology, Covenant University, Ota, Nigeria.
Mol Biol Rep. 2022 Oct;49(10):9651-9671. doi: 10.1007/s11033-022-07412-2. Epub 2022 Apr 10.
Melanoma is one of the most aggressive forms of skin cancer with a steady increase in global incidence and mortality rate over the past five decades. Paradoxically, both reduced and excessive sun exposure has been linked to increased risk of melanoma incidence and death. Although the histological classification of melanoma is useful in diagnosis, its molecular subtypes are often determined by somatic mutations, which could be UV-dependent or -independent. Multiple genes involved in cancer development are often mutated dysregulating molecular pathways with concomitant phenotypic heterogeneity. Hence, treating melanoma has been a challenge, with patients experiencing poor clinical outcomes to current therapeutic options. This presents an unmet need to understand the interaction of molecular networks underpinning melanogenesis. This review describes the crosstalk of signaling cascades in melanoma development and the putative druggable targets, with the view of elucidating newer and better therapeutic strategies for the disease.
黑色素瘤是最具侵袭性的皮肤癌之一，在过去五十年中，其全球发病率和死亡率呈稳步上升趋势。矛盾的是，减少和过度的阳光暴露都与黑色素瘤发病率和死亡率的增加有关。尽管黑色素瘤的组织学分类在诊断中很有用，但它的分子亚型通常是由体细胞突变决定的，这些突变可能与紫外线有关或无关。参与癌症发展的多个基因经常发生突变，导致分子途径失调，同时伴有表型异质性。因此，治疗黑色素瘤一直是一个挑战，患者对目前的治疗选择的临床结果不佳。这就需要我们了解黑色素生成的分子网络的相互作用。本综述描述了黑色素瘤发生过程中信号级联的相互作用以及潜在的可用药靶点，以期为该疾病阐明更新更好的治疗策略。
