Mucosal melanoma is a rare but devastating subtype of melanoma which typically has a worse prognosis than other melanoma subtypes. Large-scale next-generation sequencing studies, including our recent research, have also proved that the molecular landscape and potential oncogenic drivers of mucosal melanoma remain distinct from that of cutaneous melanoma. Recently, a number of selective cyclin-dependent kinase 4 (CDK4)/6 inhibitors have been approved for clinical application in breast cancer or entered phase III clinical trial in other solid tumors. Additionally, we have revealed that the dysregulation of cell cycle progression, caused by CDK4 amplification, is a key genetic feature in half of mucosal melanoma and targeting of CDK4 in selected mucosal melanoma patients is a potentially promising direction for precision cancer treatment by using molecular-characterized mucosal melanoma patient-derived-xenograft models. This review summarizes the current literature regarding CDK4/6 dysregulation in mucosal melanoma, preclinical and clinical studies of CDK4/6 inhibitors and potential combinational strategies in treating mucosal melanoma.

中文翻译：

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靶向细胞周期蛋白依赖性激酶 4/6 作为粘膜黑色素瘤的治疗方法。


粘膜黑色素瘤是一种罕见但具有破坏性的黑色素瘤亚型，其预后通常比其他黑色素瘤亚型更差。大规模的下一代测序研究，包括我们最近的研究，也证明粘膜黑色素瘤的分子格局和潜在致癌驱动因素仍然与皮肤黑色素瘤不同。近期，多个选择性细胞周期蛋白依赖性激酶4（CDK4）/6抑制剂已获批用于乳腺癌的临床应用或进入其他实体瘤的III期临床试验。此外，我们还发现，由 CDK4 扩增引起的细胞周期进程失调是一半粘膜黑色素瘤的关键遗传特征，在选定的粘膜黑色素瘤患者中靶向 CDK4 是通过使用分子治疗进行精准癌症治疗的潜在有希望的方向。表征了粘膜黑色素瘤患者来源的异种移植模型。本综述总结了有关粘膜黑色素瘤中 CDK4/6 失调、CDK4/6 抑制剂的临床前和临床研究以及治疗粘膜黑色素瘤的潜在组合策略的当前文献。