Liposarcoma

Targeting CDK4 (cyclin dependent kinase) amplification in liposarcoma: A comprehensive review

Tarek Assi 1Joseph Kattan 2Elie Rassy 3Hussein Nassereddine 2Fadi Farhat 2Charles Honore 4Axel Le Cesne 4Julien Adam 4Olivier Mir 4

PMID: 32593094 DOI: 10.1016/j.critrevonc.2020.103029

Affiliations

1Department of Hematology-Oncology, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon. Electronic address: tarekassi@gmail.com.

2Department of Hematology-Oncology, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon.

3Department of Hematology-Oncology, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon; French Sarcoma Group, Gustave Roussy Cancer Campus, Villejuif, France.

4French Sarcoma Group, Gustave Roussy Cancer Campus, Villejuif, France.

Abstract

Well-differentiated/dedifferentiated (WD/DD) liposarcomas, the most common form of liposarcomas, constitute up to 20 % of all soft tissue sarcomas. Several oncogenes are thought to be involved in liposarcoma pathogenesis, mainly MDM2, CDK4 and HMGA2. While MDM2 inhibitors are now tested in clinical trials, a second actionable and promising target appears to be cyclin-dependent kinase 4 (CDK4), which is amplified in up to 90 % of well differentiated or dedifferentiated (WD/DD) liposarcoma. With the paucity of available therapeutic options, the inhibition of CDK4 represent a potential therapeutic option. In this paper, we review the role of CDK4/6 inhibitors in targeting the commonly identified CDK4 amplification in WD/DD liposarcoma, with an emphasis on the published and currently ongoing trials.

Keywords: Abemaciclib; CDK4; Liposarcoma; MDM2; Palbociclib; Ribociclib; Soft tissue sarcoma.