University of Zurich, Institute of Anatomy, Zürich, Switzerland.
Stem Cells Transl Med. 2021 Apr;10(4):522-533. doi: 10.1002/sctm.20-0351. Epub 2020 Dec 1.
Melanoma is the deadliest of all skin cancers due to its high metastatic potential. In recent years, advances in targeted therapy and immunotherapy have contributed to a remarkable progress in the treatment of metastatic disease. However, intrinsic or acquired resistance to such therapies remains a major obstacle in melanoma treatment. Melanoma disease progression, beginning from tumor initiation and growth to acquisition of invasive phenotypes and metastatic spread and acquisition of treatment resistance, has been associated with cellular dedifferentiation and the hijacking of gene regulatory networks reminiscent of the neural crest (NC)-the developmental structure which gives rise to melanocytes and hence melanoma. This review summarizes the experimental evidence for the involvement of NC stem cell (NCSC)-like cell states during melanoma progression and addresses novel approaches to combat the emergence of stemness characteristics that have shown to be linked with aggressive disease outcome and drug resistance.
黑色素瘤由于其高转移潜能，是所有皮肤癌中最致命的一种。近年来，靶向治疗和免疫治疗的进展为转移性疾病的治疗带来了显著的进步。然而，对这些治疗方法的内在或获得性耐药仍然是黑色素瘤治疗的主要障碍。黑色素瘤疾病的进展，从肿瘤的起始和生长到获得侵袭表型和转移扩散以及获得治疗耐药性，与细胞去分化和基因调控网络的劫持有关，这些特征让人联想到神经嵴（NC）——发育结构，它产生黑色素细胞，从而导致黑色素瘤的发生。本综述总结了在黑色素瘤进展过程中涉及神经嵴干细胞（NCSC）样细胞状态的实验证据，并探讨了对抗出现与侵袭性疾病结局和耐药性相关的干性特征的新方法。
