@article{2ae4d02f1e984fb199a76e6007634ef0,
title = "Transient Low Doses of DNA-Demethylating Agents Exert Durable Antitumor Effects on Hematological and Epithelial Tumor Cells",
abstract = "Reversal of promoter DNA hypermethylation and associated gene silencing is an attractive cancer therapy approach. The DNA methylation inhibitors decitabine and azacitidine are efficacious for hematological neoplasms at lower, less toxic, doses. Experimentally, high doses induce rapid DNA damage and cytotoxicity, which do not explain the prolonged time to response observed in patients. We show that transient exposure of cultured and primary leukemic and epithelial tumor cells to clinically relevant nanomolar doses, without causing immediate cytotoxicity, produce an antitumor {"} memory{"} response, including inhibition of subpopulations of cancer stem-like cells. These effects are accompanied by sustained decreases in genomewide promoter DNA methylation, gene reexpression, and antitumor changes in key cellular regulatory pathways. Low-dose decitabine and azacitidine may have broad applicability for cancer management.",
author = "Tsai, {Hsing Chen} and Huili Li and {Van Neste}, Leander and Yi Cai and Carine Robert and Rassool, {Feyruz V.} and Shin, {James J.} and Harbom, {Kirsten M.} and Robert Beaty and Emmanouil Pappou and James Harris and Yen, {Ray Whay Chiu} and Nita Ahuja and Brock, {Malcolm V.} and Vered Stearns and David Feller-Kopman and Yarmus, {Lonny B.} and Lin, {Yi Chun} and Welm, {Alana L.} and Issa, {Jean Pierre} and Il Minn and William Matsui and Jang, {Yoon Young} and Sharkis, {Saul J.} and Baylin, {Stephen B.} and Zahnow, {Cynthia A.}",
note = "Funding Information: This work was, in part, supported by Grant CA 116160 from the National Institutes of Health, the Lung Spore in Cancer NCI Grant CA058184, and by funds from the Entertainment Industry Foundation and Lee Jeans, SU2C, the Samuel Waxman Cancer Research Foundation, the Irving A. Hansen Memorial Foundation (C.A.Z.), the Safeway Foundation (C.A.Z.), the Department of Defense Breast Cancer Research Program (BC075015 to A.L.W.), and The Huntsman Cancer Foundation (A.L.W.). H.-C.T. is a David Workman Student Scholar of the Samuel Waxman Cancer Research Foundation, and C.A.Z. is an Evelyn Grollman Glick Scholar. The clinical study was supported by the Cindy Rosencrans Fund for Triple Negative Breast Cancer Research. ",
year = "2012",
month = mar,
day = "20",
doi = "10.1016/j.ccr.2011.12.029",
language = "English (US)",
volume = "21",
pages = "430--446",
journal = "Cancer cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "3",
}