Identification of pharmacodynamic biomarkers and common molecular mechanisms of response to genotoxic agents in cancer cell lines.

Cancer Chemotherapy and Pharmacology
Dong-Joon MinRichard Simon

Abstract

Genotoxic agents (GAs) including cisplatin, doxorubicin, gemcitabine, and topotecan are often used in cancer treatment. However, the response to GAs is variable among patients and predictive biomarkers are inadequate to select patients for treatment. Accurate and rapid pharmacodynamics measures of response can, thus, be useful for monitoring therapy and improve clinical outcomes. This study focuses on integrating a database of genome-wide response to treatment (The NCI Transcriptional Pharmacodynamics Workbench) with a database of baseline gene expression (GSE32474) for the NCI-60 cell lines to identify mechanisms of response and pharmacodynamic (PD) biomarkers. Our analysis suggests that GA-induced endoplasmic reticulum (ER) stress may signal for GA-induced cell death. Reducing the uptake of GA, activating DNA repair, and blocking ER-stress induction cooperate to prevent GA-induced cell death in the GA-resistant cells. ATF3, DDIT3, CARS, and PPP1R15A appear as possible candidate PD biomarkers for monitoring the progress of GA treatment. Further validation studies on the proposed intrinsic drug-resistant mechanism and candidate genes are needed using in vivo data from either patient-derived xenograft models or clinical chemothe...Continue Reading

References

May 12, 2000·American Journal of Physiology. Renal Physiology·E BerginW Lieberthal
May 4, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Alexander PerathonerAlbert Amberger
Jul 25, 2006·Cancer Biology & Therapy·Melissa J Mann, Linda M Hendershot
Jan 12, 2010·Biochemical and Biophysical Research Communications·Tetsuo YamazakiHiroshi Takeshima
Feb 11, 2010·International Journal of Cell Biology·Tom VerfailliePatrizia Agostinis
Dec 15, 2010·Oncology Research·Silvia PrisleiCristiano Ferlini
Mar 3, 2011·Nature Cell Biology·Ira Tabas, David Ron
Mar 29, 2011·Cold Spring Harbor Perspectives in Biology·Ilse VandecaetsbeekJo Vanoevelen
Apr 14, 2011·International Journal of Medical Sciences·Theodor H LippertManfred Volm
Jun 28, 2011·AJR. American Journal of Roentgenology·Vahid YaghmaiRiad Salem
Aug 16, 2011·The American Journal of Pathology·Makiko KawaguchiHiroaki Kataoka
Oct 5, 2011·Journal of Experimental & Clinical Cancer Research : CR·Niels Eckstein
Jan 19, 2012·Nature Reviews. Molecular Cell Biology·Claudio Hetz
Apr 4, 2012·The Lancet Oncology·Nicholas C Turner, Jorge S Reis-Filho
Jun 27, 2012·EMBO Molecular Medicine·Nicholas A SaundersAlexander Guminski
Aug 25, 2012·Nature Reviews. Cancer·Peter Bouwman, Jos Jonkers
Sep 18, 2012·Molecular Pharmaceutics·Elodie MoysanJean-Pierre Benoit
May 28, 2013·Chemistry & Biology·Kahlin Cheung-OngCorey Nislow
Jun 26, 2013·Nature Reviews. Cancer·Hang-Ping YaoMing-Hai Wang
Aug 31, 2013·Biochimica Et Biophysica Acta·Hery UrraClaudio Hetz
Sep 7, 2013·International Journal of Molecular Sciences·Mi Jeong Kwon
Feb 4, 2014·Cancer Science·Noriko Hosoya, Kiyoshi Miyagawa
Apr 5, 2014·Human Mutation·Bernard LeroyThierry Soussi
Feb 2, 2015·The Lancet Oncology·Michelle K WilsonAmit M Oza
Feb 19, 2015·Frontiers in Oncology·Naomi DicksLuis B Agellon
Aug 1, 2015·CPT: Pharmacometrics & Systems Pharmacology·D R MouldB Frame
Sep 1, 2015·Oncotarget·Mei-Ying LiaoHan-Chung Wu

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