Targeting oncogenes to improve breast cancer chemotherapy

Cancer Research
Laura A ChristensenKaren M Vasquez

Abstract

Despite recent advances in treatment, breast cancer remains a serious health threat for women. Traditional chemotherapies are limited by a lack of specificity for tumor cells and the cell cycle dependence of many chemotherapeutic agents. Here we report a novel strategy to help overcome these limitations. Using triplex-forming oligonucleotides (TFOs) to direct DNA damage site-specifically to oncogenes overexpressed in human breast cancer cells, we show that the effectiveness of the anticancer nucleoside analogue gemcitabine can be improved significantly. TFOs targeted to the promoter region of c-myc directly inhibited gene expression by approximately 40%. When used in combination, specific TFOs increased the incorporation of gemcitabine at the targeted site approximately 4-fold, presumably due to induction of replication-independent DNA synthesis. Cells treated with TFOs and gemcitabine in combination showed a reduction in both cell survival and capacity for anchorage-independent growth (approximately 19% of untreated cells). This combination affected the tumorigenic potential of these cancer cells to a significantly greater extent than either treatment alone. This novel strategy may be used to increase the range of effectivenes...Continue Reading

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Citations

Jul 31, 2010·Biochemistry·Aklank JainKaren M Vasquez
Aug 5, 2008·Nucleic Acids Research·Maria DucaPaola B Arimondo
Aug 10, 2010·Nucleic Acids Research·Chatchawan Srisawat, David R Engelke
Jul 23, 2011·Genes & Cancer·Jinhua XuOlufunmilayo I Olopade
May 9, 2007·Breast Cancer : the Journal of the Japanese Breast Cancer Society·Kiyohiko HatakeYoshinori Ito
Oct 7, 2011·Journal of Nucleic Acids·Sudha Sharma
Apr 20, 2011·Biochimie·Anirban Mukherjee, Karen M Vasquez
Mar 19, 2014·Breast Cancer : the Journal of the Japanese Breast Cancer Society·Yu LiuPeifen Fu
Dec 12, 2012·IEEE/ACM Transactions on Computational Biology and Bioinformatics·George Papadakis, Electra Gizeli
Aug 29, 2006·Seminars in Cancer Biology·Marina Vita, Marie Henriksson
Jul 8, 2010·Biomaterials·Tsung-Lin TsaiWu-Chou Su
Mar 12, 2008·Biochimie·Aklank JainKaren M Vasquez
Jul 23, 2013·The Journal of Urology·Kyung-Chae JeongHo Kyung Seo
Apr 30, 2016·Taiwanese Journal of Obstetrics & Gynecology·Shih-Chieh LiuYen-Ying Ma
Oct 18, 2008·Expert Review of Anticancer Therapy·Yinghua Chen, Olufunmilayo I Olopade
Oct 17, 2009·Environmental Biosafety Research·Didier BreyerDirk Reheul
Aug 19, 2014·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·Chengyao XieEnhua Wang
Apr 6, 2019·Nucleic Acids Research·Imee M A Del MundoKaren M Vasquez
Oct 30, 2020·Cancer Management and Research·Feng WangWei-Bing Zhou
Jul 26, 2021·Biochimica Et Biophysica Acta. Reviews on Cancer·Nirali PandyaAmit Kumar

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