Targeting cyclin-dependent kinase 4/6 as a therapeutic approach for mucosal melanoma.
Targeting cyclin-dependent kinase 4/6 as a therapeutic approach for mucosal melanoma.
复制标题
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。
DOI：
10.1097/cmr.0000000000000777
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发表时间：
2021-12-01
影响因子：
2.2
通讯作者：
Zhang ZY
中科院分区：
文献类型：
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作者：
Shi CJ;Xu SM;Han Y;Zhou R;Zhang ZY
粘液性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，也证明了粘膜黑色素瘤的分子景观和潜在的致癌驱动因素仍然不同于皮肤黑色素瘤。近年来，一些选择性细胞周期蛋白依赖性激酶4（cyclin-dependent kinase 4，CDK4）/6抑制剂已被批准用于乳腺癌的临床治疗，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展失调是一半粘膜黑色素瘤的关键遗传特征，并且在选定的粘膜黑色素瘤患者中靶向CDK4是通过使用分子表征的粘膜黑色素瘤患者来源的异种移植模型进行精确癌症治疗的潜在有希望的方向。本文综述了CDK4/6在粘膜黑色素瘤中的失调、CDK4/6抑制剂的临床前和临床研究以及联合治疗粘膜黑色素瘤的可能策略。
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.
影响因子：
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作者：
Chen H;Li Y;Long Y;Tang E;Wang R;Huang K;Xie C;Chen G
通讯作者：
Chen G