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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A First-in-Human Phase I Study of Milademetan, an MDM2 Inhibitor, in Patients With Advanced Liposarcoma, Solid Tumors, or Lymphomas
TL;DR: In this article , the authors evaluated the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of milademetan, a small-molecule murine double minute-2 (MDM2) inhibitor, in patients with advanced cancers.
Journal ArticleDOI
Combined targeting of the p53 and pRb pathway in neuroblastoma does not lead to synergistic responses.
Nil A. Schubert,Linda Schild,Stijn van Oirschot,Kaylee M. Keller,Lindy K. Alles,Lindy Vernooij,Marloes E. Nulle,M. Emmy M. Dolman,Marlinde L. van den Boogaard,Jan J. Molenaar +9 more
TL;DR: It is concluded that p53 and pRb pathway aberrations cannot be used as predictive biomarkers for neuroblastoma sensitivity to MDM2 and/or CDK4/6 inhibitors and should be cautious with combining these inhibitors in neuroblastomas.
Patent
Companion diagnostic for cdk4 inhibitors
Andrew Koff,Aimee M. Crago,David Liu,Kovatcheva Marta,Samuel Singer,Gary K. Schwartz,Mark A. Dickson,Mary E. Klein +7 more
TL;DR: In this paper, the use of one or more biomarkers to evaluate the likelihood that a CDK4 inhibitor would produce an anti-cancer effect in a subject was proposed, which is based on the discovery that cancer treatment with a CDk4 inhibitor is more effective where treated cancer cells undergo cellular senescence rather than a transient cell cycle arrest, where cellular senesence is associated with decreased MDM2 protein level.
Journal ArticleDOI
Expression profile‑driven discovery of AURKA as a treatment target for liposarcoma
Chueh Chuan Yen,San‑Chi Chen,Giun Yi Hung,Po Kuei Wu,Wei‑Yang Chua,Yung Chan Lin,Chiao‑Han Yen,Yen‑Chun Chen,Jir You Wang,Muh Hwa Yang,Yee Chao,Ming Chau Chang,Wei Ming Chen +12 more
TL;DR: The findings of the present study suggested the potential of AURKA as a therapeutic target in LPS cell line models, while the novel combination of AurKA inhibitors and chemotherapy requires further investigation.
Journal ArticleDOI
A Multi-Modality Treatment of Retroperitoneal De-Differentiated Liposarcoma
Joel Horowitz,Mayank Singhal,Dana A. Marrero,Fuad Bashjawish,Dezarae Leto,Maryselle Winters,Julian Jeberaeel +6 more
TL;DR: Achieving complete resection and the grade of the tumor at diagnosis are the 2 most important prognostic factors for patient survival in retroperitoneal liposarcoma, as survival rates are inversely proportional to the gradeof the tumor.
References
More filters
Journal ArticleDOI
New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1)
Elizabeth Eisenhauer,P. Therasse,Jan Bogaerts,Lawrence H. Schwartz,Daniel J. Sargent,Robert Ford,Janet Dancey,S. Arbuck,S. Gwyther,Margaret M. Mooney,Larry Rubinstein,Lalitha K. Shankar,Lori E. Dodd,Robert M. Kaplan,Denis Lacombe,Jaap Verweij +15 more
TL;DR: The revised RECIST includes a new imaging appendix with updated recommendations on the optimal anatomical assessment of lesions, and a section on detection of new lesions, including the interpretation of FDG-PET scan assessment is included.
Book
Statistical methods for rates and proportions
TL;DR: In this paper, the basic theory of Maximum Likelihood Estimation (MLE) is used to detect a difference between two different proportions of a given proportion in a single proportion.
Journal ArticleDOI
Statistical Methods for Rates and Proportions.
B. S. Everitt,Joseph L. Fleiss +1 more
Journal Article
[New response evaluation criteria in solid tumours-revised RECIST guideline (version 1.1)].
Hirokazu Watanabe,Morihito Okada,Yasushi Kaji,Miyako Satouchi,Yozo Sato,Yuichiro Yamabe,Hiroaki Onaya,Masahiro Endo,Miyuki Sone,Yasuaki Arai +9 more
TL;DR: This paper is an overview of the new response evaluation criteria in solid tumours: revised RECIST guideline (version 1. 1), with a focus on updated contents.
Journal Article
Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts
David W. Fry,Patricia J. Harvey,Paul R. Keller,William Elliott,Maryanne Meade,Erin Trachet,Mudher Albassam,Xianxian Zheng,Wilbur R. Leopold,Nancy Pryer,Peter L. Toogood +10 more
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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