文章：

通过PKC抑制葡萄膜黑色素瘤靶向GNAQ/11

Targeting GNAQ/11 through PKC inhibition in uveal melanoma 

原文发布日期：2022-02-18 

英文摘要：

Uveal melanoma is a rare malignancy affecting 5.1 patients/million per year with definitive treatment options of enucleation or radiation therapy to the primary tumor. Unfortunately, no FDA-approved systemic therapies exist for patients in the adjuvant or metastatic setting. Molecular profiling over the past decade has helped define uveal melanomas by characteristic mutations: GNAQ, GNA11, BAP1, SF3B1, and EIF1AX mutations. GNAQ/11 mutations are present in over 90% of patients with uveal melanoma and lead to signal transduction through G-protein coupled receptors to downstream growth factors. PKC inhibition has been an active area of investigation targeting this pathway specific to uveal melanoma. Several molecules have been developed and evaluated in clinical trials. Responses have been noted but clinical development has also yielded multiple toxicities and pathways of resistance limiting both breadth and durability of responses leading to combination therapy approaches. PKC inhibition remains an active and encouraging area of research to determine effective therapies for patients with uveal melanoma. 

摘要翻译：

葡萄膜黑色素瘤是一种罕见恶性肿瘤，每年发病率为5.1例/百万人，主要治疗方案包括眼球摘除术或原发性肿瘤放射治疗。遗憾的是，目前FDA尚未批准任何用于辅助或转移性治疗的全身性治疗方案。过去十年的分子谱研究已通过特征性突变界定葡萄膜黑色素瘤：GNAQ、GNA11、BAP1、SF3B1和EIF1AX基因突变。超过90%的葡萄膜黑色素瘤患者存在GNAQ/11突变，这些突变通过G蛋白偶联受体向下游生长因子进行信号转导。针对葡萄膜黑色素瘤特有的这条通路，PKC抑制一直是重点研究领域。多个分子药物已被开发并在临床试验中评估，虽然观察到治疗反应，但临床开发过程中也出现多种毒性反应和耐药通路，限制了反应的广度和持久性，从而促使联合治疗方法的出现。PKC抑制仍是确定葡萄膜黑色素瘤有效疗法的重要且令人鼓舞的研究领域。

原文链接：

Targeting GNAQ/11 through PKC inhibition in uveal melanoma