UTHealth McGovern Medical School, Houston, TX 77030, USA.
Department of Dermatology, UTHealth McGovern Medical School, Houston, TX 77030, USA.
Int J Mol Sci. 2024 Oct 15;25(20):11055. doi: 10.3390/ijms252011055.
Although rare, Merkel cell carcinoma (MCC) is a highly aggressive and increasingly prevalent neuroendocrine cancer of the skin. While current interventions, including surgical resection, radiation, and immunotherapy have been employed in treating many patients, those who remain unresponsive to treatment are met with sparse alternatives and a grim prognosis. For this reason, it is of interest to expand the repertoire of available therapies for MCC patients who remain resistant to current primary interventions. Recently, our improved mechanistic understanding of aberrant cell signaling observed in both MCPyV-positive and -negative MCC has facilitated exploration into several small molecules and inhibitors, among them receptor tyrosine kinase inhibitors (TKIs) and somatostatin analogs (SSAs), both of which have positively improved response rates and reduced tumor volumes upon application to treatment of MCC. The introduction of such targeted therapies into treatment protocols holds promise for more personalized care tailored towards patients of diverse subtypes, thereby improving outcomes and mitigating tumor burden, especially for treatment-resistant individuals. In this review, we characterize recent findings surrounding targeted treatments that have been applied to MCC and provide an overview of emerging perspectives on translatable options that can be further developed to offer additional therapeutic avenues for patients with the disease.
虽然罕见,但 Merkel 细胞癌(MCC)是一种高度侵袭性且日益流行的皮肤神经内分泌癌。目前已经采用了包括手术切除、放疗和免疫疗法在内的多种干预措施来治疗许多患者,但对于那些对治疗无反应的患者,治疗方法选择有限,预后不佳。因此,对于那些对当前主要干预措施仍然耐药的 MCC 患者,扩大可用治疗方法的范围是很有意义的。最近,我们对 MCPyV 阳性和阴性 MCC 中观察到的异常细胞信号的机制理解的提高,促进了对几种小分子和抑制剂的探索,其中包括受体酪氨酸激酶抑制剂(TKIs)和生长抑素类似物(SSAs),这两种抑制剂在应用于 MCC 治疗时均能提高缓解率并减少肿瘤体积。将这些靶向治疗引入治疗方案有望为不同亚型的患者提供更个性化的治疗,从而改善预后并减轻肿瘤负担,特别是对于耐药患者。在这篇综述中,我们描述了最近应用于 MCC 的靶向治疗的发现,并概述了可进一步开发以提供疾病患者额外治疗途径的新兴可转化选择的观点。