scholarly journals Histone Deacetylase Inhibitors and Epigenetic Modifications as a Novel Strategy in Renal Cell Carcinoma

2013 ◽  
Vol 19 (4) ◽  
pp. 333-340 ◽  
Author(s):  
Swathi Ramakrishnan ◽  
Roberto Pili
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Histone Deacetylase ◽  
Renal Cell ◽  
Histone Deacetylase Inhibitors ◽  
Epigenetic Modifications ◽  
Novel Strategy

Decreased Acetylation of Histone H3 in Renal Cell Carcinoma: A Potential Target of Histone Deacetylase Inhibitors

2008 ◽  
Vol 180 (3) ◽  
pp. 1131-1136 ◽  
Author(s):  
Kent Kanao ◽  
Shuji Mikami ◽  
Ryuichi Mizuno ◽  
Toshiaki Shinojima ◽  
Masaru Murai ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Histone Deacetylase ◽  
Renal Cell ◽  
Histone Deacetylase Inhibitors ◽  
Histone H3 ◽  
Potential Target

1010: Histone Deacetylase Inhibitors Suppress Expression of the Apoptosis Inhibitor Survivin in Renal Cell Carcinoma Cells

2004 ◽  
Vol 171 (4S) ◽  
pp. 267-267
Author(s):  
Markus Mueller ◽  
Steffen Weikert ◽  
Axel Mussier ◽  
Hans Krause ◽  
Kurt Miller
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Histone Deacetylase ◽  
Renal Cell ◽  
Histone Deacetylase Inhibitors ◽  
Carcinoma Cells ◽  
Apoptosis Inhibitor

B7-H1 glycoprotein blockade: A novel strategy to enhance immunotherapy in patients with renal cell carcinoma

Urology ◽  
2005 ◽  
Vol 66 (5) ◽  
pp. 10-14 ◽  
Author(s):  
R. Houston Thompson ◽  
W. Scott Webster ◽  
John C. Cheville ◽  
Christine M. Lohse ◽  
Haidong Dong ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Novel Strategy

scholarly journals Sunitinib Dose Escalation Overcomes Transient Resistance in Clear Cell Renal Cell Carcinoma and Is Associated with Epigenetic Modifications

2014 ◽  
Vol 14 (2) ◽  
pp. 513-522 ◽  
Author(s):  
Remi Adelaiye ◽  
Eric Ciamporcero ◽  
Kiersten Marie Miles ◽  
Paula Sotomayor ◽  
Jonathan Bard ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Dose Escalation ◽  
Renal Cell ◽  
Clear Cell ◽  
Epigenetic Modifications ◽  
Cell Renal Cell Carcinoma

Phase I/II study of high-dose interleukin 2, aldesleukin, in combination with the histone deacetylase inhibitor entinostat in patients with metastatic renal cell carcinoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS4687-TPS4687
Author(s):  
Roberto Pili ◽  
Li Shen ◽  
Saby George ◽  
Hans Hammers ◽  
Anita Sandecki ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Phase I ◽  
Cell Carcinoma ◽  
Histone Deacetylase ◽  
Dose Level ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Interleukin 2 ◽  
High Dose ◽  
Correlative Studies

TPS4687 Background: Immunosuppressive factors such as regulatory T cells (Tregs) limit the efficacy of immunotherapies. Histone deacetylase (HDAC) inhibitors have been shown to have anti-tumor activity in different malignancies and to induce immuno-modulatory effects. We have previously reported that a class I specific HDAC inhibitor, entinostat, has synergistic anti-tumor effect in combination with high dose interleukin-2 (IL-2) in a renal cell carcinoma model (Kato Y et al Clinical Cancer Res 2007). Our group has also recently showed that low dose entinostat induces STAT3 acetylation, down-regulates Foxp3 expression in Tregs, and blocks Tregs suppressive function without affecting T effector cells (Shen Li et al PLoSONE 2012). Methods: Based on these preclinical evidences we have initiated a Phase I/II clinical study with entinostat and high dose IL-2 in patients with metastatic renal cell carcinoma. The primary objective of the study is to evaluate the safety, tolerability and efficacy of this combination strategy. The main eligibility criteria are clear cell histology, no prior treatments and being fit to receive high dose IL-2. The Phase I portion consists of two dose levels of entinostat (3 and 5 mg) and a fixed standard dose of IL-2 (600,000 units/Kg every 8 hrs.) according to a 3+3 design. The sample size of 36 patients in the Phase II portion is powered to detect an increase in objective response rate from 20% to 40% as compared to historical data with high dose IL-2 alone. Correlative studies include assessment of CD4+, CD8+, CD4+/Foxp3, NK cells in tumor and blood samples by immunohistochemistry and FACS analysis, and tumor metabolism by FDG PET. We are also exploring the relationship between entinostat exposure with pharmacodynamic endpoints. To date dose level one has been completed without DLT. Enrollment to dose level two has begun in the Fall 2011. The results from this study may confirm the role of entinostat in enhancing the effect of IL-2 and may be translated into other combination strategies involving immunotherapies. The clinical trial and correlative studies are supported by the National Cancer Institute- R21CA137649.

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