Pedersen Elisabeth A, Verhaegen Monique E, Joseph Mallory K, Harms Kelly L, Harms Paul W
Department of Dermatology, University of Michigan, Ann Arbor, MI, United States.
Department of Pathology, University of Michigan, Ann Arbor, MI, United States.
Front Oncol. 2024 Jul 29;14:1413793. doi: 10.3389/fonc.2024.1413793. eCollection 2024.
Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine carcinoma thought to arise via either viral (Merkel cell polyomavirus) or ultraviolet-associated pathways. Surgery and radiotherapy have historically been mainstays of management, and immunotherapy has improved outcomes for advanced disease. However, there remains a lack of effective therapy for those patients who fail to respond to these established approaches, underscoring a critical need to better understand MCC biology for more effective prognosis and treatment. Here, we review the fundamental aspects of MCC biology and the recent advances which have had profound impact on management. The first genetically-engineered mouse models for MCC tumorigenesis provide opportunities to understand the potential MCC cell of origin and may prove useful for preclinical investigation of novel therapeutics. The MCC cell of origin debate has also been advanced by recent observations of MCC arising in association with a clonally related hair follicle tumor or squamous cell carcinoma . These studies also suggested a role for epigenetics in the origin of MCC, highlighting a potential utility for this therapeutic avenue in MCC. These and other therapeutic targets form the basis for a wealth of ongoing clinical trials to improve MCC management. Here, we review these recent advances in the context of the existing literature and implications for future investigations.
默克尔细胞癌（MCC）是一种侵袭性皮肤神经内分泌癌，被认为是通过病毒（默克尔细胞多瘤病毒）或紫外线相关途径发生的。手术和放疗历来是主要的治疗手段，免疫疗法改善了晚期疾病的治疗效果。然而，对于那些对这些既定方法无反应的患者，仍然缺乏有效的治疗方法，这突出表明迫切需要更好地了解MCC生物学，以实现更有效的预后和治疗。在此，我们回顾MCC生物学的基本方面以及对治疗产生深远影响的最新进展。首个用于MCC肿瘤发生的基因工程小鼠模型为了解潜在的MCC起源细胞提供了机会，并可能对新型疗法的临床前研究有用。最近观察到MCC与克隆相关的毛囊肿瘤或鳞状细胞癌相关发生，这也推动了MCC起源细胞的争论。这些研究还表明表观遗传学在MCC起源中起作用，凸显了这一治疗途径在MCC中的潜在效用。这些以及其他治疗靶点构成了大量正在进行的改善MCC治疗的临床试验的基础。在此，我们结合现有文献回顾这些最新进展以及对未来研究的意义。
