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Open AccessJournal ArticleDOI

Phase II Trial of the CDK4 Inhibitor PD0332991 in Patients With Advanced CDK4-Amplified Well-Differentiated or Dedifferentiated Liposarcoma

Mark A. Dickson, +13 more
- 01 Jun 2013 - 
- Vol. 31, Iss: 16, pp 2024-2028
TLDR
Treatment with theCDK4 inhibitor PD0332991 was associated with a favorable progression-free rate in patients with CDK4-amplified and RB-expressing WDLS/DDLS who had progressive disease despite systemic therapy.
Abstract: 
Purpose CDK4 is amplified in 90% of well-differentiated (WDLS) and dedifferentiated liposarcomas (DDLS). The selective cyclin-dependent kinase 4 (CDK4)/CDK6 inhibitor PD0332991 inhibits growth and induces senescence in cell lines and xenografts. In a phase I trial of PD0332991, several patients with WDLS or DDLS experienced prolonged stable disease. We performed an open-label phase II study to determine the safety and efficacy of PD0332991 in patients with advanced WDLS/DDLS.

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Journal ArticleDOI

RB1 dual role in proliferation and apoptosis: cell fate control and implications for cancer therapy

Paola Indovina, +5 more
- 18 Jun 2015 - 
TL;DR: An overview of the possible underlying molecular mechanisms whereby RB1, and its family members, dictate cell fate in various contexts, and the current antitumoral strategies aimed at the use of RB1 as predictive, prognostic and therapeutic target in cancer are described.
Journal ArticleDOI

MiR-506 suppresses proliferation and induces senescence by directly targeting the CDK4/6-FOXM1 axis in ovarian cancer

Guoyan Liu, +14 more
- 01 Jul 2014 - 
TL;DR: It is found that deregulation of miR‐506 in ovarian carcinoma promotes an aggressive phenotype, and it is demonstrated that CDK4 and CDK6 are direct targets of mi R‐506, and that miR-506 can inhibit CDK 4/6–FOXM1 signalling, which is activated in the majority of serous ovarian carcinomas.
Journal ArticleDOI

Retroperitoneal liposarcoma: current insights in diagnosis and treatment.

Lucas Matthyssens, +2 more
- 10 Feb 2015 - 
TL;DR: Current insights and controversies regarding histology, molecular biology, extent of surgery, (neo)adjuvant treatment, and systemic treatment including novel targeted agents in RLS are reviewed.
Journal ArticleDOI

Highlights of the Latest Advances in Research on CDK Inhibitors

Jonas Cicenas, +6 more
- 27 Oct 2014 - 
TL;DR: The recent advance of selective CDK inhibitors allowed the first successful efforts to target these kinases for the therapies of several diseases to be targeted.
Journal ArticleDOI

Antiproliferative Effects of CDK4/6 Inhibition in CDK4-Amplified Human Liposarcoma In Vitro and In Vivo

Yi Xiang Zhang, +12 more
- 01 Sep 2014 - 
TL;DR: Findings validate the critical role of CDK4 in maintaining liposarcoma proliferation through its ability to inactivate RB function, and suggest its potential function in the regulation of survival and metabolism of liposARcoma, supporting the rationale for clinical development of LEE011 for the treatment of WD/DDLPS.
References
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Journal Article

Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts

David W. Fry, +10 more
- 01 Nov 2004 - 
TL;DR: Results indicate that inhibition of Cdk4/6 alone is sufficient to cause tumor regression and a net reduction in tumor burden in some tumors.
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