scholarly journals Pharmacological blockade of ASCT2-dependent glutamine transport leads to antitumor efficacy in preclinical models

2018 ◽  
Vol 24 (2) ◽  
pp. 194-202 ◽  
Author(s):  
Michael L Schulte ◽  
Allie Fu ◽  
Ping Zhao ◽  
Jun Li ◽  
Ling Geng ◽  
...  
Keyword(s):  
Antitumor Efficacy ◽  
Preclinical Models ◽  
Glutamine Transport ◽  
Pharmacological Blockade

scholarly journals #2714, a novel active inhibitor with potent G2/M phase arrest and antitumor efficacy in preclinical models

2018 ◽  
Vol 4 (1) ◽  
Author(s):  
Wen-Jie Lu ◽  
Wen Peng ◽  
Qian-Qian Sun ◽  
Yong-Huai Li ◽  
Bo Chen ◽  
...  
Keyword(s):  
Antitumor Efficacy ◽  
Preclinical Models ◽  
Active Inhibitor ◽  
Phase Arrest ◽  
M Phase

scholarly journals Pharmacokinetic and pharmacodynamic analysis of fulvestrant in preclinical models of breast cancer to assess the importance of its estrogen receptor-α degrader activity in antitumor efficacy

2019 ◽  
Vol 179 (1) ◽  
pp. 67-77 ◽  
Author(s):  
Suzanne E. Wardell ◽  
Alexander P. Yllanes ◽  
Christina A. Chao ◽  
Yeeun Bae ◽  
Kaitlyn J. Andreano ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Kinase Inhibitors ◽  
Single Agent ◽  
Metastatic Breast ◽  
Estrogen Receptor Α ◽  
Antitumor Efficacy ◽  
Preclinical Models ◽  
Preclinical Development ◽  
Exposure Levels

Abstract Purpose Fulvestrant is a selective estrogen receptor downregulator (SERD) that is approved for first- or second-line use as a single agent or in combination with cyclin dependent kinase or phosphatidylinositol 3-kinase inhibitors for the treatment of metastatic breast cancer. Fulvestrant exhibits exceptionally effective antitumor activity in preclinical models of breast cancer, a success that has been attributed to its robust SERD activity despite modest receptor downregulation in patient tumors. By modeling human exposures in animal models we probe the absolute need for SERD activity. Methods Three xenograft models of endocrine therapy-resistant breast cancer were used to evaluate the efficacy of fulvestrant administered in doses historically used in preclinical studies in the field or by using a dose regimen intended to model clinical exposure levels. Pharmacokinetic and pharmacodynamic analyses were conducted to evaluate plasma exposure and intratumoral ER downregulation. Results A clinically relevant 25 mg/kg dose of fulvestrant exhibited antitumor efficacy comparable to the historically used 200 mg/kg dose, but at this lower dose it did not result in robust ER downregulation. Further, the antitumor efficacy of the lower dose of fulvestrant was comparable to that observed for other oral SERDs currently in development. Conclusion The use of clinically unachievable exposure levels of fulvestrant as a benchmark in preclinical development of SERDs may negatively impact the selection of those molecules that are advanced for clinical development. Further, these studies suggest that antagonist efficacy, as opposed to SERD activity, is likely to be the primary driver of clinical response.

scholarly journals Dual Promoter–Controlled Oncolytic Adenovirus CG5757 Has Strong Tumor Selectivity and Significant Antitumor Efficacy in Preclinical Models

2005 ◽  
Vol 11 (24) ◽  
pp. 8845-8855 ◽  
Author(s):  
Yuanhao Li ◽  
Neeraja Idamakanti ◽  
Trini Arroyo ◽  
Steve Thorne ◽  
Tony Reid ◽  
...  
Keyword(s):  
Oncolytic Adenovirus ◽  
Antitumor Efficacy ◽  
Preclinical Models ◽  
Tumor Selectivity ◽  
Dual Promoter
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