CRO Aviano National Cancer Institute IRCCS, 33081 Aviano, Italy.
Department of Medicine (DAME), University of Udine, 33100 Udine, Italy.
Cells. 2021 May 28;10(6):1334. doi: 10.3390/cells10061334.
Historically, metastatic melanoma was considered a highly lethal disease. However, recent advances in drug development have allowed a significative improvement in prognosis. In particular, BRAF/MEK inhibitors and anti-PD1 antibodies have completely revolutionized the management of this disease. Nonetheless, not all patients derive a benefit or a durable benefit from these therapies. To overtake this challenges, new clinically active compounds are being tested in the context of clinical trials. CDK4/6 inhibitors are drugs already available in clinical practice and preliminary evidence showed a promising activity also in melanoma. Herein we review the available literature to depict a comprehensive landscape about CDK4/6 inhibitors in melanoma. We present the molecular and genetic background that might justify the usage of these drugs, the preclinical evidence, the clinical available data, and the most promising ongoing clinical trials.
从历史上看，转移性黑色素瘤被认为是一种高度致命的疾病。然而，最近药物开发方面的进展使得预后有了显著改善。特别是，BRAF/MEK 抑制剂和抗 PD-1 抗体彻底改变了这种疾病的治疗方法。尽管如此，并非所有患者都能从这些治疗中受益或获得持久的益处。为了克服这些挑战，新的具有临床活性的化合物正在临床试验中进行测试。CDK4/6 抑制剂是已经在临床实践中应用的药物，初步证据表明它们在黑色素瘤中也具有有前景的活性。本文综述了相关文献，以全面描述 CDK4/6 抑制剂在黑色素瘤中的应用。我们介绍了可能证明这些药物使用合理性的分子和遗传背景、临床前证据、临床可用数据以及最有前途的正在进行的临床试验。
