Targeting cyclin-dependent kinase 4/6 as a therapeutic approach for mucosal melanoma.

Abstract

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.

• Authors: Chao-Ji Shi, Sheng-Ming Xu, Yong Han, Rong Zhou, Zhi-Yuan Zhang
• Journal: Melanoma research (Melanoma Res) Vol. 31 Issue 6 Pg. 495-503 (12 01 2021) ISSN: 1473-5636 [Electronic] England
• PMID: 34483306 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.

Chemical References

• Cyclin-Dependent Kinase 4
• Cyclin-Dependent Kinase 6

Topics

• Animals
• Cyclin-Dependent Kinase 4 (pharmacology, therapeutic use)
• Cyclin-Dependent Kinase 6 (pharmacology, therapeutic use)
• Disease Models, Animal
• Humans
• Melanoma (drug therapy)
• Mice
• Mouth Neoplasms (drug therapy)
• Prognosis
• Skin Neoplasms (drug therapy)