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. * Dr. Zhi-yuan Zhang and Dr. Rong Zhou contributed equally to the writing of this article. Received 17 April 2021 Accepted 2 August 2021 Correspondence to Zhi-yuan Zhang, PhD, Department of Oral Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, No. 639, Zhizaoju Rd, Shanghai 200011, China, E-mail: Zhiyuan.Zhang@sh9hospital.org.cn This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
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