Phase II Trial of the CDK4 Inhibitor PD0332991 in Patients With Advanced CDK4-Amplified Well-Differentiated or Dedifferentiated Liposarcoma
Mark A. Dickson,William D. Tap,Mary Louise Keohan,Sandra P. D'Angelo,Mrinal M. Gounder,Cristina R. Antonescu,Jonathan Landa,Li-Xuan Qin,Dustin D. Rathbone,Mercedes M. Condy,Yelena Ustoyev,Aimee M. Crago,Samuel Singer,Gary K. Schwartz +13 more
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.read more
Citations
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FOXM1 in sarcoma: role in cell cycle, pluripotency genes and stem cell pathways
TL;DR: Current systemic treatment of sarcoma is of limited efficacy and inhibiting FOXM1 represents a potential new strategy, according to this work.
Journal ArticleDOI
Cyclin-dependent kinase 11 (CDK11) is crucial in the growth of liposarcoma cells.
Bin Jia,Edwin Choy,Gregory M. Cote,David C. Harmon,Shunan Ye,Quancheng Kan,Henry J. Mankin,Francis J. Hornicek,Zhenfeng Duan +8 more
TL;DR: Investigation of the functional and therapeutic relevance of cyclin-dependent kinase 11 as a putative target in liposarcoma suggests that CDK11 is critical for the growth and proliferation of liposARcoma cells.
Journal ArticleDOI
Palbociclib-induced autophagy and senescence in gastric cancer cells
TL;DR: It is shown that, similar to mammary cells, gastric cancer cells are sensitive to the CDK4/6 inhibitor Palbociclib, an indication that autophagy in these experimental settings represents an adaptive mechanism that promotes cell survival rather than being an effector mechanism of senescence.
Journal ArticleDOI
Expression and therapeutic implications of cyclin-dependent kinase 4 (CDK4) in osteosarcoma.
Yubing Zhou,Jacson Shen,Zujiang Yu,Francis J. Hornicek,Quancheng Kan,Zhenfeng Duan,Zhenfeng Duan +6 more
TL;DR: CDK4 inhibition by either palbociclib or specific small interference RNA (siRNA) exhibited dose-dependent inhibition of osteosarcoma cell proliferation and growth, accompanied by suppression of the CDK4/6-cyclinD-Rb signaling pathway.
Journal ArticleDOI
CDKN2A/p16 Loss Implicates CDK4 as a Therapeutic Target in Imatinib-Resistant Dermatofibrosarcoma Protuberans
Grant Eilers,Jeffrey T. Czaplinski,Mark Mayeda,Nacef Bahri,Derrick Tao,Meijun Zhu,Jason L. Hornick,Neal I. Lindeman,Ewa Sicinska,Andrew J. Wagner,Jonathan A. Fletcher,Adrián Mariño-Enríquez +11 more
TL;DR: CDK4/6 inhibition is a preclinically effective treatment against p16-negative, imatinib-resistant FS-DFSP, and should be evaluated as a therapeutic strategy in patients with unresectable or metastatic imatinIB-resistant DFSP.
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