Epigenetics as a Therapeutic Target in Breast Cancer

Connolly, Roisin; Stearns, Vered

doi:10.1007/s10911-012-9263-3

Cited by 117Epigenetics and DNA MethylationHistone Deacetylase Inhibitors ResearchGenomics and Chromatin Dynamics

Epigenetics as a Therapeutic Target in Breast Cancer

Open access

Connolly, Roisin, Stearns, Vered·2012·Journal of Mammary Gland Biology and Neoplasia

DOI 10.1007/s10911-012-9263-3PMC PMC3515719

Open this paper in CoChat — free account

Abstract

Epigenetics refers to alterations in gene expression due to modifications in histone acetylation and DNA methylation at the promoter regions of genes. Unlike genetic mutations, epigenetic alterations are not due to modifications in the gene primary nucleotide sequence. The importance of epigenetics in the initiation and progression of breast cancer has led many investigators to incorporate this novel and exciting field in breast cancer drug development. Several drugs that target epigenetic alterations, including inhibitors of histone deacetylase (HDAC) and DNA methyltransferase (DNMT), are currently approved for treatment of hematological malignancies and are available for clinical investigation in solid tumors. In this manuscript, we review the critical role of epigenetics in breast cancer including the potential for epigenetic alterations to serve as biomarkers determining breast cancer prognosis and response to therapy. We highlight initial promising results to date with use of epigenetic modifiers in patients with breast cancer and the ongoing challenges involved in the successful establishment of these agents for the treatment of breast cancer.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1007/s10911-012-9263-3

Cites

98 of 98 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Epigenetic modification alters gene expression leading to endocrine therapy resistance and may be reversed by epigenetic modifiers such as histone deacetylase (HDAC) inhibitors.
“Epigenetic modification alters gene expression leading to endocrine therapy resistance and may be reversed by epigenetic modifiers such as histone deacetylase (HDAC) inhibitors.6-8”
From E2112: Randomized Phase III Trial of Endocrine Therapy Plus Entinostat or Placebo in Hormone Receptor–Positive Advanced Breast Cancer. A Trial of the ECOG-ACRIN Cancer Research Group (2021) · cites this paper as [6]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

1 retracted

RETRACTED ARTICLE: 5-Aza-Deoxycytidine Induces Selective Degradation of DNA Methyltransferase 1 by a Proteasomal Pathway That Requires the KEN Box, Bromo-Adjacent Homology Domain, and Nuclear Localization Signal
Ghoshal, K., Datta, J., Majumder, S., Bai, S., Kutay, H., Motiwala, T., & Jacob, S. T. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.11.4727-4741.2005 · Cited by 431 · see citing works
Retracted
New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1)
Eisenhauer, E. A., Therasse, P., Bogaerts, J., Schwartz, L. H., Sargent, D., Ford, R., Dancey, J., Arbuck, S., Gwyther, S., Mooney, M., et al. (2009) · European Journal of Cancer · doi:10.1016/j.ejca.2008.10.026 · Cited by 29,534 · see citing works
Molecular portraits of human breast tumours
Perou, C., Sørlie, T., Eisen, M., van de Rijn, M., Jeffrey, S., Rees, C. A., Pollack, J., Ross, D., Johnsen, H., Akslen, L., et al. (2000) · Nature · doi:10.1038/35021093 · Cited by 16,551 · see citing works
Translating the Histone Code
Jenuwein, T., & Allis, C. D. (2001) · Science · doi:10.1126/science.1063127 · Cited by 9,756 · see citing works
DNA Methyltransferases Dnmt3a and Dnmt3b Are Essential for De Novo Methylation and Mammalian Development
Okano, M., Bell, D. W., Haber, D. A., & Li, E. (1999) · Cell · doi:10.1016/s0092-8674(00)81656-6 · Cited by 6,143 · see citing works
The fundamental role of epigenetic events in cancer
Jones, P. A., & Baylin, S. B. (2002) · Nature Reviews Genetics · doi:10.1038/nrg816 · Cited by 5,648 · see citing works
Inhibition of Poly(ADP-Ribose) Polymerase in Tumors from <i>BRCA</i> Mutation Carriers
Fong, P. C., Boss, D. S., Yap, T. A., Tutt, A., Wu, P., Mergui-Roelvink, M., Mortimer, P., Swaisland, H., Lau, A., O'Connor, M. J., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0900212 · Cited by 3,634 · see citing works
Gene Silencing in Cancer in Association with Promoter Hypermethylation
Herman, J. G., & Baylin, S. B. (2003) · New England Journal of Medicine · doi:10.1056/nejmra023075 · Cited by 3,414 · see citing works
Guidelines for the Evaluation of Immune Therapy Activity in Solid Tumors: Immune-Related Response Criteria
Wolchok, J. D., Hoos, A., O'Day, S. J., Weber, J. S., Hamid, O., Lebbé, C., Maio, M., Binder, M., Bohnsack, O., Nichol, G. M., et al. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-1624 · Cited by 3,214 · see citing works
Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study
Fenaux, P., Mufti, G. J., Hellstrom-Lindberg, E., Santini, V., Finelli, C., Giagounidis, A., Schoch, R., Gattermann, N., Sanz, G., List, A., et al. (2009) · The Lancet Oncology · doi:10.1016/s1470-2045(09)70003-8 · Cited by 2,663 · cited 1× · see citing works
“This reflects what is observed clinically in patients with hematologic malignancies treated with these agents [29, 84].”
Inactivation of the DNA-Repair Gene MGMT and the Clinical Response of Gliomas to Alkylating Agents
Esteller, M., García‐Foncillas, J., Andion, E., Goodman, S. N., Hidalgo, O. F., Vanaclocha, V., Baylin, S. B., & Herman, J. G. (2000) · New England Journal of Medicine · doi:10.1056/nejm200011093431901 · Cited by 2,256 · see citing works
Cancer epigenomics: DNA methylomes and histone-modification maps
Esteller, M. (2007) · Nature Reviews Genetics · doi:10.1038/nrg2005 · Cited by 2,150 · see citing works
Cellular differentiation, cytidine analogs and DNA methylation
Jones, P. A., & Taylor, S. M. (1980) · Cell · doi:10.1016/0092-8674(80)90237-8 · Cited by 1,831 · see citing works
Phase IIB Multicenter Trial of Vorinostat in Patients With Persistent, Progressive, or Treatment Refractory Cutaneous T-Cell Lymphoma
Olsen, E. A., Kim, Y. H., Kuzel, T. M., Pacheco, T. R., Foss, F. M., Parker, S. R. S., Frankel, S. R., Chen, C., Ricker, J. L., Arduino, J. M., et al. (2007) · Journal of Clinical Oncology · doi:10.1200/jco.2006.10.2434 · Cited by 1,057 · see citing works
Phase I Study of an Oral Histone Deacetylase Inhibitor, Suberoylanilide Hydroxamic Acid, in Patients With Advanced Cancer
Kelly, W. K., O’Connor, O. A., Krug, L. M., Chiao, J. H., Heaney, M. L., Curley, T., MacGregor‐Cortelli, B., Tong, W. P., Secrist, J. P., Schwartz, L. B., et al. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.14.167 · Cited by 906 · see citing works
Worms gang up on bacteria
Jones, R. (2002) · Nature Reviews Genetics · doi:10.1038/nrg962 · Cited by 828 · see citing works
Phase II Multi-Institutional Trial of the Histone Deacetylase Inhibitor Romidepsin As Monotherapy for Patients With Cutaneous T-Cell Lymphoma
Piekarz, R., Frye, R., Turner, M. L. C., Wright, J. J., Allen, S. L., Kirschbaum, M. H., Zain, J. M., Prince, H. M., Leonard, J. P., Geskin, L. J., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2008.21.6150 · Cited by 739 · see citing works
Combination Epigenetic Therapy Has Efficacy in Patients with Refractory Advanced Non–Small Cell Lung Cancer
Juergens, R. A., Wrangle, J. M., Vendetti, F. P., Murphy, S. C., Zhao, M., Coleman, B., Sebree, R., Rodgers, K., Hooker, C. M., Franco, N. C., et al. (2011) · Cancer Discovery · doi:10.1158/2159-8290.cd-11-0214 · Cited by 686 · see citing works
Final Results From a Multicenter, International, Pivotal Study of Romidepsin in Refractory Cutaneous T-Cell Lymphoma
Whittaker, S. J., Demierre, M., Kim, E. J., Rook, A. H., Lerner, A., Duvic, M. A., Scarisbrick, J. J., Reddy, S. A., Robak, T., Becker, J. C., et al. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2010.28.9066 · Cited by 666 · see citing works
Transient Low Doses of DNA-Demethylating Agents Exert Durable Antitumor Effects on Hematological and Epithelial Tumor Cells
Tsai, H.-C., Li, H., Neste, L. V., Cai, Y., Robert, C., Rassool, F. V., Shin, J., Harbom, K., Beaty, R. M., Pappou, E. P., et al. (2012) · Cancer Cell · doi:10.1016/j.ccr.2011.12.029 · Cited by 651 · see citing works
Self-citation
DNA Methylation Markers and Early Recurrence in Stage I Lung Cancer
Brock, M. V., Hooker, C. M., Ota-Machida, E., Han, Y. K., Guo, M., Ames, S., Glöckner, S. C., Piantadosi, S., Gabrielson, E. W., Pridham, G., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0706550 · Cited by 594 · see citing works
Phase 2 trial of romidepsin in patients with peripheral T-cell lymphoma
Piekarz, R., Frye, R., Prince, H. M., Kirschbaum, M. H., Zain, J. M., Allen, S. L., Jaffe, E. S., Ling, A. L., Turner, M. L. C., Peer, C. J., et al. (2011) · Blood · doi:10.1182/blood-2010-10-312603 · Cited by 487 · see citing works
Combined DNA Methyltransferase and Histone Deacetylase Inhibition in the Treatment of Myeloid Neoplasms
Gore, S. D., Baylin, S. B., Sugar, E. A., Carraway, H. E., Miller, C. B., Carducci, M. A., Grever, M. R., Galm, O., Dauses, T., Karp, J. E., et al. (2006) · Cancer Research · doi:10.1158/0008-5472.can-06-0080 · Cited by 475 · see citing works
Inhibition of histone deacetylase increases cytotoxicity to anticancer drugs targeting DNA.
Kim, M. S., Blake, M., Baek, J. H., Kohlhagen, G., Pommier, Y. G., & Carrier, F. (2003) · PubMed · Cited by 464 · see citing works
DNA methylation and breast carcinogenesis
Widschwendter, M., & Jones, P. A. (2002) · Oncogene · doi:10.1038/sj.onc.1205606 · Cited by 457 · see citing works
Synergistic activation of functional estrogen receptor (ER)-alpha by DNA methyltransferase and histone deacetylase inhibition in human ER-alpha-negative breast cancer cells.
Yang, X., Phillips, D. L., Ferguson, A. T., Nelson, W. G., Herman, J. G., & Davidson, N. E. (2001) · PubMed · Cited by 419 · see citing works
A phase II study of the histone deacetylase inhibitor vorinostat combined with tamoxifen for the treatment of patients with hormone therapy-resistant breast cancer
Munster, P. N., Thurn, K. T., Thomas, S., Raha, P., Lacevic, M., Miller, A., Melisko, M., Ismail-Khan, R., Rugo, H., Moasser, M., et al. (2011) · British Journal of Cancer · doi:10.1038/bjc.2011.156 · Cited by 391 · see citing works
The histone deacetylase inhibitor suberoylanilide hydroxamic acid induces differentiation of human breast cancer cells.
Münster, P. N., Troso-Sandoval, T. A., Rosen, N. X., Rifkind, R. A., Marks, P. A., & Richon, V. M. (2001) · PubMed · Cited by 368 · see citing works
Clinical Studies of Histone Deacetylase Inhibitors
Prince, H. M., Bishton, M. J., & Harrison, S. J. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-08-2785 · Cited by 358 · see citing works
Multicenter Study of Decitabine Administered Daily for 5 Days Every 4 Weeks to Adults With Myelodysplastic Syndromes: The Alternative Dosing for Outpatient Treatment (ADOPT) Trial
Steensma, D. P., Baer, M. R., Slack, J. L., Buckstein, R. J., Godley, L. A., Garcia‐Manero, G., Albitar, M. X., Larsen, J. S., Arora, S., Cullen, M. T., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2008.19.6550 · Cited by 319 · see citing works
HDAC6 Expression Is Correlated with Better Survival in Breast Cancer
Zhang, Z., Yamashita, H., Toyama, T., Sugiura, H., Omoto, Y., Ando, Y., Mita, K., Hamaguchi, M., Hayashi, S., & Iwase, H. (2004) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-04-0455 · Cited by 295 · see citing works
Independent Review of E2100: A Phase III Trial of Bevacizumab Plus Paclitaxel Versus Paclitaxel in Women With Metastatic Breast Cancer
Gray, R. J., Bhattacharya, S., Bowden, C., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2008.21.6630 · Cited by 295 · see citing works
Quantitative Multiplex Methylation-Specific PCR Assay for the Detection of Promoter Hypermethylation in Multiple Genes in Breast Cancer
Fackler, M. J., McVeigh, M., Mehrotra, J., Blum, M. A., Lange, J. R., Lapides, A., Garrett, E., Argani, P., & Sukumar, S. V. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-3341 · Cited by 270 · see citing works
Histone deacetylase inhibitor LAQ824 down-regulates Her-2 and sensitizes human breast cancer cells to trastuzumab, taxotere, gemcitabine, and epothilone B.
Fuino, L., Bali, P., Wittmann, S., Donapaty, S., Guo, F., Yamaguchi, H., Wang, H., Atadja, P. W., & Bhalla, K. N. (2003) · PubMed · Cited by 261 · see citing works
DNA methylation of RASSF1A, HIN‐1, RAR‐β, Cyclin D2 and Twist in in situ and invasive lobular breast carcinoma
Fackler, M. J., McVeigh, M., Evron, E., Garrett, E., Mehrotra, J., Polyák, K., Sukumar, S. V., & Argani, P. (2003) · International Journal of Cancer · doi:10.1002/ijc.11508 · Cited by 253 · see citing works
Circulating Micro-RNAs as Potential Blood-Based Markers for Early Stage Breast Cancer Detection
Schrauder, M. G., Strick, R., Schulz‐Wendtland, R., Strissel, P. L., Kahmann, L., Loehberg, C. R., Lux, M. P., Jud, S. M., Hartmann, A., Hein, A., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0029770 · Cited by 250 · see citing works
A Phase II Trial of Vorinostat (Suberoylanilide Hydroxamic Acid) in Metastatic Breast Cancer: A California Cancer Consortium Study
Luu, T. H., Morgan, R. J., Leong, L., Lim, D. W., McNamara, M., Portnow, J., Frankel, P. H., Smith, D. D., Doroshow, J. H., Gandara, D. R., et al. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-08-0122 · Cited by 237 · see citing works
Histone deacetylase-1 and -3 protein expression in human breast cancer: a tissue microarray analysis
Krusche, C. A., W�lfing, P., Kersting, C., Vloet, A. J., B�cker, W., Kiesel, L., Beier, H. M., & Alfer, J. (2005) · Breast Cancer Research and Treatment · doi:10.1007/s10549-004-1668-2 · Cited by 230 · see citing works
DNA methylation profiling reveals a predominant immune component in breast cancers
Dedeurwaerder, S., Desmedt, C., Calonne, E., Singhal, S. K., Haibe‐Kains, B., Defrance, M., Michiels, S., Volkmar, M., Deplus, R., Luciani, J., et al. (2011) · EMBO Molecular Medicine · doi:10.1002/emmm.201100801 · Cited by 225 · see citing works
Fifteen-year results of a randomized phase III trial of fenretinide to prevent second breast cancer
Veronesi, U., Mariani, L., DeCensi, A., et al. (2006) · Annals of Oncology · doi:10.1093/annonc/mdl047 · Cited by 217 · see citing works
5-Aza-2′-deoxycytidine-mediated reductions in G9A histone methyltransferase and histone H3 K9 di-methylation levels are linked to tumor suppressor gene reactivation
Wozniak, R. J., Klimecki, W. T., Lau, S. S., Feinstein, Y., & Futscher, B. W. (2006) · Oncogene · doi:10.1038/sj.onc.1209763 · Cited by 213 · see citing works
CpG Island Hypermethylation of Tumor Suppressor microRNAs in Human Cancer
Lujambio, A. (2007) · Cell Cycle · doi:10.4161/cc.6.12.4408 · Cited by 211 · see citing works
DNMT3A mutations and response to the hypomethylating agent decitabine in acute myeloid leukemia
Metzeler, K. H., Walker, A., Geyer, S. M., Garzon, R., Klisovic, R. B., Bloomfield, C. D., Blum, W. G., & Marcucci, G. (2011) · Leukemia · doi:10.1038/leu.2011.342 · Cited by 208 · see citing works
Restoration of Tamoxifen Sensitivity in Estrogen Receptor–Negative Breast Cancer Cells: Tamoxifen-Bound Reactivated ER Recruits Distinctive Corepressor Complexes
Sharma, D., Saxena, N. K., Davidson, N. E., & Vertino, P. M. (2006) · Cancer Research · doi:10.1158/0008-5472.can-06-0402 · Cited by 208 · see citing works
Mapping of ER gene CpG island methylation-specific polymerase chain reaction.
Lapidus, R. G., Nass, S. J., Butash, K. A., Parl, F. F., Weitzman, S. A., Graff, J. R., Herman, J. G., & Davidson, N. E. (1998) · PubMed · Cited by 206 · see citing works
Genome-wide high throughput analysis of DNA methylation in eukaryotes
Pomraning, K., Smith, K., & Freitag, M. (2008) · Methods · doi:10.1016/j.ymeth.2008.09.022 · Cited by 203 · see citing works
CpG Island Hypermethylation of Tumor Suppressor Genes in Human Cancer
Herranz, M., & Esteller, M. (2007) · Springer eBooks · doi:10.1007/0-387-27443-x_6 · Cited by 202 · see citing works
Genome-wide Methylation Analysis Identifies Genes Specific to Breast Cancer Hormone Receptor Status and Risk of Recurrence
Fackler, M. J., Umbricht, C. B., Williams, D., Argani, P., Cruz, L.-A., Merino, V. F., Teo, W. W., Zhang, Z., Huang, P., Visvananthan, K., et al. (2011) · Cancer Research · doi:10.1158/0008-5472.can-11-1630 · Cited by 201 · see citing works
Phase I and Pharmacokinetic Study of Vorinostat, A Histone Deacetylase Inhibitor, in Combination with Carboplatin and Paclitaxel for Advanced Solid Malignancies
Ramalingam, S. S., Parise, R. A., Ramananthan, R. K., Lagattuta, T. F., Musguire, L. A., Stoller, R. G., Potter, D. M., Argiris, A. E., Zwiebel, J. A., Egorin, M. J., et al. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-0162 · Cited by 193 · see citing works
Hypomethylation of the synuclein gamma gene CpG island promotes its aberrant expression in breast carcinoma and ovarian carcinoma.
Gupta, A., Godwin, A. K., Vanderveer, L., et al. (2003) · PubMed · Cited by 184 · see citing works
Activity of Suberoylanilide Hydroxamic Acid Against Human Breast Cancer Cells with Amplification of Her-2
Bali, P., Pranpat, M., Swaby, R. F., Fiskus, W. C., Yamaguchi, H., Balasis, M. E., Rocha, K., Wang, H., Richon, V. M., & Bhalla, K. N. (2005) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-05-0344 · Cited by 184 · see citing works
Phase 1b‐2a study to reverse platinum resistance through use of a hypomethylating agent, azacitidine, in patients with platinum‐resistant or platinum‐refractory epithelial ovarian cancer
Fu, S., Hu, W., Iyer, R. B., Kavanagh, J. J., Coleman, R. L., Levenback, C. F., Sood, A. K., Wolf, J. K., Gershenson, D. M., Markman, M. M., et al. (2010) · Cancer · doi:10.1002/cncr.25701 · Cited by 183 · see citing works
BRCA1 CpG Island Hypermethylation Predicts Sensitivity to Poly(Adenosine Diphosphate)- Ribose Polymerase Inhibitors
Veeck, J., Ropero, S., Setién, F., González‐Suárez, E., Osório, A., Benitez, J. J., Herman, J. G., & Esteller, M. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2010.30.1010 · Cited by 173 · see citing works
Phase I trial of vorinostat and doxorubicin in solid tumours: histone deacetylase 2 expression as a predictive marker
Münster, P. N., Marchion, D. C., Thomas, S., Egorin, M. J., Minton, S., Springett, G. M., Lee, J.-H., Simon, G. R., Chiappori, A., Sullivan, D. M., et al. (2009) · British Journal of Cancer · doi:10.1038/sj.bjc.6605293 · Cited by 167 · see citing works
Suberoylanilide Hydroxamic Acid as a Potential Therapeutic Agent for Human Breast Cancer Treatment
Huang, L., & Pardee, A. B. (2000) · Molecular Medicine · doi:10.1007/bf03401823 · Cited by 164 · see citing works
Genome-Wide DNA Methylation Profiling of CpG Islands in Breast Cancer Identifies Novel Genes Associated with Tumorigenicity
Hill, V. K., Ricketts, C. J., Bièche, I., Vacher, S., Gentle, D., Lewis, C. M., Maher, E. R., & Latif, F. (2011) · Cancer Research · doi:10.1158/0008-5472.can-10-4026 · Cited by 163 · see citing works
Functional Activation of the Estrogen Receptor-α and Aromatase by the HDAC Inhibitor Entinostat Sensitizes ER-Negative Tumors to Letrozole
Sabnis, G. J., Goloubeva, O. G., Chumsri, S., Nguyen, N., Sukumar, S. V., & Brodie, A. M. H. (2011) · Cancer Research · doi:10.1158/0008-5472.can-10-2458 · Cited by 160 · see citing works
Epigenetic Drug Discovery: Targeting DNA Methyltransferases
Foulks, J. M., Parnell, K. M., Nix, R. N., Chau, S., Świerczek, K., Saunders, M. J., Wright, K., Hendrickson, T. F., Ho, K.-K., McCullar, M. V., et al. (2011) · SLAS DISCOVERY · doi:10.1177/1087057111421212 · Cited by 160 · see citing works
Selective Inhibitors of Histone Methyltransferase DOT1L: Design, Synthesis, and Crystallographic Studies
Yao, Y., Chen, P., Diao, J., Cheng, G., Deng, L., Anglin, J. L., Prasad, B. V. V., & Song, Y. (2011) · Journal of the American Chemical Society · doi:10.1021/ja206312b · Cited by 157 · see citing works
S110, a 5-Aza-2′-Deoxycytidine–Containing Dinucleotide, Is an Effective DNA Methylation Inhibitor In vivo and Can Reduce Tumor Growth
Chuang, J. C., Warner, S. L., Vollmer, D. L., Vankayalapati, H., Redkar, S., Bearss, D. J., Qiu, X., Yoo, C. B., & Jones, P. A. (2010) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-09-1048 · Cited by 157 · see citing works
Expression of Hypoxia-Inducible Factor-1α, Histone Deacetylase 1, and Metastasis-Associated Protein 1 in Pancreatic Carcinoma
Miyake, K., Yoshizumi, T., Imura, S., Sugimoto, K., Batmunkh, E., Kanemura, H., Morine, Y., & Shimada, M. (2008) · Pancreas · doi:10.1097/mpa.0b013e31815f2c2a · Cited by 155 · see citing works
A Novel Histone Deacetylase Inhibitor, Scriptaid, Enhances Expression of Functional Estrogen Receptor α (ER) in ER negative human breast cancer cells in combination with 5-aza 2′-deoxycytidine
Keen, J. C., Lan, Y., Mack, K. M., Pettit, C., Smith, D., Sharma, D., & Davidson, N. E. (2003) · Breast Cancer Research and Treatment · doi:10.1023/a:1026146524737 · Cited by 150 · see citing works
Phase 2 clinical trial of 5-azacitidine, valproic acid, and all-trans retinoic acid in patients with high-risk acute myeloid leukemia or myelodysplastic syndrome
Raffoux, E., Cras, A., Recher, C., Boëlle, P.-Y., de Labarthe, A., Turlure, P., Marolleau, J.-P., Reman, O., Gardin, C., Victor, M., et al. (2010) · Oncotarget · doi:10.18632/oncotarget.106 · Cited by 134 · see citing works
Effect of Cytarabine and Decitabine in Combination in Human Leukemic Cell Lines
Qin, T., Youssef, E. M., Jelı́nek, J., Chen, R., Yang, A. S., Garcia‐Manero, G., & Issa, J. J. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-2762 · Cited by 134 · see citing works
Inhibitors of histone demethylation and histone deacetylation cooperate in regulating gene expression and inhibiting growth in human breast cancer cells
Huang, Y., Vasilatos, S. N., Boric, L., Shaw, P. G., & Davidson, N. E. (2011) · Breast Cancer Research and Treatment · doi:10.1007/s10549-011-1480-8 · Cited by 132 · see citing works
Bcl-xL and Bcl-2 expression in squamous cell carcinoma of the head and neck
Pena, J. C., Thompson, C. B., Recant, W. M., Vokes, E. E., & Rudin, C. M. (1999) · Cancer · doi:10.1002/(sici)1097-0142(19990101)85:1 · Cited by 132 · see citing works
Histone modifications dictate specific biological readouts
Munshi, A., Shafi, G., Aliya, N., & Jyothy, A. (2009) · Journal of genetics and genomics/Journal of Genetics and Genomics · doi:10.1016/s1673-8527(08)60094-6 · Cited by 130 · see citing works
ERα negative breast cancer cells restore response to endocrine therapy by combination treatment with both HDAC inhibitor and DNMT inhibitor
Fan, J., Yin, W.-J., Lu, J.-S., Wang, L., Wu, J., Wu, F.-Y., Di, G.-H., Shen, Z.-Z., & Shao, Z.-M. (2008) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-008-0354-x · Cited by 129 · see citing works
Phase 1 study of epigenetic priming with decitabine prior to standard induction chemotherapy for patients with AML
Scandura, J. M., Roboz, G. J., Moh, M., Morawa, E., Brenet, F. A., Bose, J. R., Villegas, L. J., Gergis, U. S., Mayer, S. A., Ippoliti, C. M., et al. (2011) · Blood · doi:10.1182/blood-2010-11-320093 · Cited by 129 · see citing works
Chemoprevention of carcinogen-induced mammary tumorigenesis by the hybrid polar cytodifferentiation agent, suberanilohydroxamic acid (SAHA).
Cohen, L. A., Amin, S., Marks, P. A., Rifkind, R. A., Desai, D. H., & Richon, V. M. (1999) · PubMed · Cited by 112 · see citing works
Inhibition of histone deacetylase enhances the anti-proliferative action of antiestrogens on breast cancer cells and blocks tamoxifen-induced proliferation of uterine cells
Hodges-Gallagher, L., Valentine, C. D., Bader, S. E., & Kushner, P. J. (2006) · Breast Cancer Research and Treatment · doi:10.1007/s10549-006-9459-6 · Cited by 105 · see citing works
Impact of the putative differentiating agent sodium phenylbutyrate on myelodysplastic syndromes and acute myeloid leukemia.
Gore, S. D., Weng, L. J., Zhai, S., et al. (2001) · PubMed · Cited by 102 · see citing works
Phase I Study of Decitabine in Combination with Vorinostat in Patients with Advanced Solid Tumors and Non-Hodgkin's Lymphomas
Stathis, A., Hotte, S. J., Chen, E. X., et al. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-1893 · Cited by 100 · see citing works
Will Dna Methylation Inhibitors Work In Solid Tumors? A Review Of The Clinical Experience With Azacitidine And Decitabine In Solid Tumors
Cowan, L. A., Talwar, S., & Yang, A. S. (2010) · Epigenomics · doi:10.2217/epi.09.44 · Cited by 98 · see citing works
Phase I–II study of vorinostat plus paclitaxel and bevacizumab in metastatic breast cancer: evidence for vorinostat-induced tubulin acetylation and Hsp90 inhibition in vivo
Ramaswamy, B., Fiskus, W. C., Cohen, B., Pellegrino, C. A., Hershman, D. L., Chuang, E., Luu, T. H., Somlo, G., Goetz, M. P., Swaby, R. F., et al. (2011) · Breast Cancer Research and Treatment · doi:10.1007/s10549-011-1928-x · Cited by 88 · see citing works
Self-citation
Histone Deacetylase Inhibitors: From Chromatin Remodeling to Experimental Cancer Therapeutics
Arts, J. J. G., Schepper, S. D., & Emelen, K. V. (2003) · Current Medicinal Chemistry · doi:10.2174/0929867033456657 · Cited by 83 · see citing works
Inhibition of histone deacetylase suppresses EGF signaling pathways by destabilizing EGFR mRNA in ER-negative human breast cancer cells
Zhou, Q., Shaw, P. G., & Davidson, N. E. (2008) · Breast Cancer Research and Treatment · doi:10.1007/s10549-008-0148-5 · Cited by 70 · see citing works
Methylation-Specific PCR
Licchesi, J. D. F., & Herman, J. G. (2008) · Methods in molecular biology · doi:10.1007/978-1-59745-522-0_22 · Cited by 68 · see citing works
Methylation Profiling of Benign and Malignant Breast Lesions and Its Application to Cytopathology
Pu, R. T., Laitala, L. E., Alli, P. M., et al. (2003) · Modern Pathology · doi:10.1097/01.mp.0000095782.79895.e2 · Cited by 65 · see citing works
Evidence that Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand Induction by 5-Aza-2′-Deoxycytidine Sensitizes Human Breast Cancer Cells to Adriamycin
Xu, J., Zhou, J., Tainsky, M. A., & Wu, G. S. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-2310 · Cited by 54 · see citing works
RASSF1A and CDH1 hypermethylation as potential epimarkers in breast cancer
Sebova, K., Zmetakova, I., Bella, V., Kajo, K., Stankovicova, I., Kajabova, V., Krivulcik, T., Lasabová, Z., Tomka, M., Galbavý, Š., et al. (2011) · Cancer Biomarkers · doi:10.3233/cbm-2012-0230 · Cited by 52 · see citing works
Association of aberrant DNA methylation with clinicopathological features in breast cancer
Tserga, A. (2011) · Oncology Reports · doi:10.3892/or.2011.1576 · Cited by 51 · see citing works
Mammalian DNA methyltransferases prefer poly(dI-dC) as substrate.
Pedrali‐Noy, G., & Weissbach, A. (1986) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)57438-5 · Cited by 50 · see citing works
Hypermethylated Genes as Biomarkers of Cancer in Women with Pathologic Nipple Discharge
Fackler, M. J., Rivers, A., Teo, W. W., et al. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-08-1981 · Cited by 49 · see citing works
Phase II study of 5-azacytidine in solid tumors.
Weiss, A. J., Metter, G. E., Nealon, T. F., et al. (1977) · PubMed · Cited by 49 · see citing works
HDAC inhibitor SNDX-275 enhances efficacy of trastuzumab in erbB2-overexpressing breast cancer cells and exhibits potential to overcome trastuzumab resistance
Huang, X., Wang, S., Lee, C., Yang, X., & Liu, B. (2011) · Cancer Letters · doi:10.1016/j.canlet.2011.03.019 · Cited by 47 · see citing works
Phase I study of 5-azacytidine (NSC-102816) .
Weiss, A. J., Stambaugh, J. E., Mastrangelo, M. J., et al. (1972) · PubMed · Cited by 43 · see citing works
Phase II trial of 13-cis-retinoic acid in metastatic breast cancer
Cassidy, J., Lippman, M. E., Lacroix, A., et al. (1982) · European Journal of Cancer and Clinical Oncology · doi:10.1016/0277-5379(82)90239-5 · Cited by 43 · see citing works
MicroRNAs: Toward the Clinic for Breast Cancer Patients
Ferracin, M., Querzoli, P., Călin, G. A., & Negrini, M. (2011) · Seminars in Oncology · doi:10.1053/j.seminoncol.2011.08.005 · Cited by 34 · see citing works
Mechanisms of suberoylanilide hydroxamic acid inhibition of mammary cell growth
Said, T. K., Moraes, R., Sinha, R., & Medina, D. (2000) · Breast Cancer Research · doi:10.1186/bcr284 · Cited by 17 · see citing works
Alteration of DNA Methylation Status in K562 and MCF-7 Cancer Cell Lines by Nucleoside Analogues
Krawczyk, B., & Fabianowska‐Majewska, K. (2006) · Nucleosides Nucleotides & Nucleic Acids · doi:10.1080/15257770600890764 · Cited by 17 · see citing works
The Effects of Nucleoside Analogues on Promoter Methylation of Selected Tumor Suppressor Genes in MCF-7 and MDA-MB-231 Breast Cancer Cell Lines
Krawczyk, B., Rudnicka, K., & Fabianowska‐Majewska, K. (2007) · Nucleosides Nucleotides & Nucleic Acids · doi:10.1080/15257770701509594 · Cited by 16 · see citing works
Abstract 4666: A phase 2 study investigating the safety, efficacy and surrogate biomarkers of response of 5-azacitidine (5-AZA) andentinostat (MS-275) in patients with triple-negative advanced breast cancer.
Connolly, R. M., Jankowitz, R. C., Zahnow, C. A., et al. (2013) · Cancer Research · doi:10.1158/1538-7445.am2013-4666 · Cited by 15 · see citing works
Self-citation
PD01-04: Entinostat, a Novel Histone Deacetylase Inhibitor, Added to Exemestane Improves PFS in Advanced Breast Cancer in a Randomized, Phase II, Double-Blind Study.
Yardley, D. A., Ismail-Khan, R., & Klein, P. (2011) · Cancer Research · doi:10.1158/0008-5472.sabcs11-pd01-04 · Cited by 10 · see citing works
OT3-01-06: A Phase 2 Study Investigating the Safety, Efficacy and Surrogate Biomarkers of Response of 5-Azacitidine (5-AZA) and Entinostat (MS-275) in Patients with Advanced Breast Cancer.
Connolly, R., Jankowitz, R., Andreopoulou, E., et al. (2011) · Cancer Research · doi:10.1158/0008-5472.sabcs11-ot3-01-06 · Cited by 8 · see citing works
Self-citation
Association of vorinostat with decrease in gene expression of proliferation-related genes in tumors from women with newly diagnosed breast cancer.
Stearns, V., Jacobs, L. K., Tsangaris, T. N., et al. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2010.28.15_suppl.3097 · Cited by 4 · see citing works
Self-citation
Early change in 18-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET) to predict response to preoperative systemic therapy (PST) in HER2-negative primary operable breast cancer: Translational breast cancer research consortium (TBCRC008).
Connolly, R. M., Leal, J. P., Goetz, M. P., et al. (2012) · Journal of Clinical Oncology · doi:10.1200/jco.2012.30.15_suppl.10509 · Cited by 4 · see citing works
Self-citation
Abstract PR-6: Pharmacodynamic analysis of ENCORE 301, a placebo-controlled, randomized phase 2 study of exemestane with and without entinostat in postmenopausal ER+ breast cancer patients demonstrates an association of lysine hyperacetylation with clinical outcome.
Ordentlich, P. (2011) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.targ-11-pr-6 · Cited by 3 · see citing works

Flagged first, then by citations

Sorted by citations

Entinostat: a promising treatment option for patients with advanced breast cancer
Connolly, R. M., Rudek, M. A., & Piekarz, R. (2017) · Future Oncology · doi:10.2217/fon-2016-0526 · Cited by 148 · see citing works
Self-citation
E2112: Randomized Phase III Trial of Endocrine Therapy Plus Entinostat or Placebo in Hormone Receptor–Positive Advanced Breast Cancer. A Trial of the ECOG-ACRIN Cancer Research Group
Connolly, R. M., Zhao, F., Miller, K. D., Lee, M.-J., Piekarz, R. L., Smith, K. L., Brown-Glaberman, U. A., Winn, J. S., Faller, B. A., Onitilo, A. A., et al. (2021) · Journal of Clinical Oncology · doi:10.1200/jco.21.00944 · Cited by 125 · see citing works
Self-citation
Secreted phospholipases A2 are differentially expressed and epigenetically silenced in human breast cancer cells
Brglez, V., Pucer, A., Pungerčar, J., Lambeau, G., & Petan, T. (2014) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2014.01.182 · Cited by 35 · see citing works

A combined approach for the study of histone deacetylase inhibitors
Činčárová, L., Lochmanová, G., Nováková, K., Šultesová, P., Konečná, H., Fajkusová, L., Fajkus, J., & Zdráhal, Z. (2012) · Molecular BioSystems · doi:10.1039/c2mb25136a · Cited by 22 · see citing works
The Crosstalk between Acetylation and Phosphorylation: Emerging New Roles for HDAC Inhibitors in the Heart
Habibian, J. S., & Ferguson, B. S. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms20010102 · Cited by 57 · see citing works
Epigenetic Therapy for Breast Cancer
Cai, F., Kohler, C., Zhang, B., Wang, M., Chen, W., & Zhong, X. (2011) · International Journal of Molecular Sciences · doi:10.3390/ijms12074465 · Cited by 46 · see citing works
Epigenetic Therapy with Histone Deacetylase Inhibitors: Implications for Cancer Treatment
(2021) · Frontiers research topics · doi:10.3389/978-2-88966-835-9
Targeting epigenetic abnormalities with histone deacetylase inhibitors
Conley, B. A., Wright, J. J., & Kummar, S. (2006) · Cancer · doi:10.1002/cncr.22064 · Cited by 39 · see citing works

Authors: Connolly, R., & Stearns, V.
Affiliations: Johns Hopkins University (US)
Corresponding author: Stearns, Vered
ORCID: Stearns, Vered
Venue: Journal of Mammary Gland Biology and Neoplasia
Publisher: Springer Science and Business Media LLC
Published: 2012-07-27
Volume: 17
Issue: 3-4
Pages: 191-204
ISSN: 1083-3021 (ISSN-L)
1573-7039
DOI: 10.1007/s10911-012-9263-3
PMC: PMC3515719
OpenAlex: W2074336595
Cited by: 117
References: 98
Citations by year: 2026: 3 · 2025: 3 · 2023: 5 · 2022: 3 · 2021: 4 · 2020: 13 · 2019: 8 · 2018: 11 · 2017: 7 · 2016: 17 · 2015: 18 · 2014: 11 · 2013: 9 · 2012: 5
FWCI: 1.23
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Journal of Mammary Gland Biology and Neoplasia (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Cancer Institute (P50CA088843)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords: epigenetics, breast cancer, histone deacetylase inhibitors, hypomethylating agents, histone acetylation, DNA methylation, epigenetic biomarkers, prognosis, treatment response, epigenetic regulators, drug development
MeSH terms: Antineoplastic Agents, Breast Neoplasms, Female, Humans, DNA Methylation, Epigenesis, Genetic

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Epigenetics as a Therapeutic Target in Breast Cancer

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Self-check

Cites

Cited by

Related

Record

About these checks