Syndax Pharmaceuticals Key Publications


Epigenetics

April 7, 2012. "Cancer's epicentre." The Economist. pgs89-90.

Arrowsmith, C.H., C. Bountra, et al. "Epigenetic protein families: a new frontier for drug discovery." Nature Drug Disc. 11:384-400.

Baylin, S. and P.A. Jones (2010). "Epigenetic drugs take on cancer." Science. 330:576-578.

Esteller (2008). "Molecular origins of cancer: epigenetics in cancer." New England J Med 2008;358:1148-59.

Jones, P.A. and S. Baylin (2007). "The epigenetics of cancer." Cell. 128:683-92.

HDACi

Bradner, J.E., N. West, et al (2010). "Chemical phylogenetics of histone deacetylases." Nat Chem Biol. 6(March): 238-43.

Lane, A.A. and B.A. Bradner (2009). "Histone deacetylase inhibitors in cancer therapy." J Clin Onc. 27(32):5459-68.

Lee, M.J., Y.S. Kim, et al (2008). "Histone deacetylase inhibitors in cancer therapy." Curr Opin Oncol. 20(6):639-49.

Singh, A. and J. Settelman (2010). "EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer." Oncogene. 29:4741-51.

Witt, O., H.E. Deubzer, et al (2009). "HDAC family: What are the cancer relevant targets?" Cancer Lett. 277:8-21.

HDACi / DNMTi

Cameron, E.E., K.E. Bachman, et al. (1999). "Synergy of demethylation and histone deacetylase inhibition in the re-expression of genes silenced in cancer." Nature Gen. 21:103-07.

Ganesan, A., L. Nolan, et al (2009). " Epigenetic Therapy: Histone Acetylation, DNA Methylation and Anti-Cancer Drug Discovery." Curr Cancer Drug Targets. 9:963-81.

Gore, Steven D. (2009). "In vitro basis for treatment with hypomethylating agents and histone deacetylase inhibitors: can epigenetic changes be used to monitor treatment?" Leuk Res 33(Suppl.2): S2–S6.

Kaiser, J. (2010) "Epigenetics drugs take on cancer." Science. 330:576-78.

Stearns, V., Q. Zhou, et al (2007). "Epigenetic regulation as a new target for breast cancer therapy." Canc Invest. 25:659–65.

Zhou, Q., A.T. Agoston, et al. (2008). "Inhibition of histone deacetylases promotes ubiquitin-dependent proteasomal degradation of DNA methyltransferase 1 in human breast cancer cells." Mol Cancer Res. 6(5):873-83.

HDACi / DNMTi / Lung Cancer

Belinsky, S., M. Grimes, et al. (2011). "Combination therapy with vidaza and entinostat suppresses tumor growth and reprograms the epigenome in an orthotopic lung cancer model." Cancer Res. 71(2):OF1-9.

Juergens, R., J. Wrangle, et al. (2011). "Combination epigenetic therapy has efficacy in patients with refractory advanced non–small cell lung cancer." Cancer Discovery. OF1-10.

Juergens, R.A., and C.M. Rudin (2013). "Aberrant Epigenetic Regulation: A Central Contributor to Lung Carcinogenesis and a New Therapeutic Target." ASCO Educational Book.

Rodriquez-Paredes, M. and M. Esteller. (2011). "A Combined epigenetic therapy equals the efficacy of conventional chemotherapy in refractory advanced non-small cell lung cancer." Cancer Discovery. OF1-3.

Entinostat / HDACi / Lung Cancer

Coldren, C.D., B.A. Helfrich, et al. (2006). "Baseline gene expression predicts sensitivity to gefitinib in non–small cell lung cancer cell lines." Mol Cancer Res. 4(8):521-28.

Dannenberg, J-H. and A. Berns (2010). "Drugging drug resistance." Cell. 141:18-20.

Kakihana, M., T. Ohira, et al. (2009). "Induction of E-cadherin in lung cancer and interaction with growth suppression by histone deacetylase inhibition." J Thor Oncology. 4(12):1455-65.

Lee, M.J., A. Adjei, et al. (2009). "Pharmacokinetic and pharmacodynamic analysis of patients treated with the histone deacetylase inhibitor entinostat in combination with erlotinib." AACR Mol Targets Meeting Poster B206.

Neal, J.W. and L.V. Sequist (2012). "Complex role of histone deacetylase inhibitors in the treatment of non-small-cell lung cancer." JCO, ahead of print. 30:1-3.

Sharma, S.V., D.Y. Lee, et al. (2010). "A chromatin-mediated reversible drug-tolerant state in cancer cell subpopulations." Cell. 141:69-80.

Suda, K., K.Tomizawa, et al. (2011) "Epithelial to mesenchymal transition in an epidermal growth factor receptor-mutant lung cancer cell line with acquired resistance to erlotinib." J Thor Onc. 6(7):1-10.

Thomson, et al. (2005). "Epithelial to mesenchymal transition is a determinant of sensitivity of non–small-cell lung carcinoma cell lines and xenografts to epidermal growth factor receptor inhibition." Cancer Res. 65(20):9455-62.

Witta, S., R.M. Jotte, et al. (2012) "Randomized Phase II Trial of Erlotinib With and Without Entinostat in Patients With Advanced Non–Small-Cell Lung Cancer Who Progressed on Prior Chemotherapy." JCO 30(18):2248-2255

Witta, S.E., R. Dziadziuszko, et al. (2009). "ErbB-3 expression is associated with E-cadherin and their coexpression restores response to gefitinib in non-small-cell lung cancer SCLC)." Annals Onc. 1-7.

Witta, S.E., R.M. Gemmill, et al. (2006). "Restoring E-cadherin expression increases sensitivity to epidermal growth factor receptor inhibitors in lung cancer cell lines." Cancer Res 66(2): 944-50.

Workman, P. and J. Travers. (2010). "Drug-tolerant insurgents." Nature. 464:844-85.

Yauch, R.L., T. Januario, et al. (2005). "Epithelial versus mesenchymal phenotype determines in vitro sensitivity and predicts clinical activity of erlotinib in lung cancer patients." Clin Cancer Res. 11(24):8686-98.

Entinostat / HDACi / Breast Cancer

Bicaku, E., D.C. Marchion, et al. (2008). "Selective inhibition of histone deacetylase 2 silences progesterone receptor-mediated signaling." Cancer Res. 68(5):1513-9.

Brodie, A., L. Macedo, et al. (2010). "Aromatase resistance mechanisms in model systems in vivo." J Steroid Biochem Mol Biol. 118:283-87.

Chia, S., W. Gradishar, et al. (2008). "Double-blind, randomized placebo controlled trial of fulvestrant compared with exemestane after prior nonsteroidal aromatase inhibitor therapy in postmenopausal women with hormone receptor–positive, advanced breast cancer: results from EFECT." 26(10):1664-70.

Chumsri, S., T. Howes, et al. (2011). "Aromatase, aromatase inhibitors, and breast cancer." J Steroid Biochem Mol Biol. 125:13-22.

Connolly, R., and V. Stearns (2012). "Epigenetics as a therapeutic target in breast cancer." J Mammary Gland Biol Neoplasia. Published on-line 27July2012.

Hodges-Gallagher, L., C.D. Valentine, et al. (2007). "Inhibition of histone deacetylase enhances the anti-proliferative action of antiestrogens on breast cancer cells and blocks tamoxifen-induced proliferation of uterine cells." Breast Cancer Res Treat. 105(3):297-309.

Lustberg, M.B. and B. Ramaswamy. (2009). "Epigenetic targeting in breast cancer: therapeutic impact and future direction." Drug News Perspect. 22(7):369-81.

O’Brien et al (2011). ""Breast cancer stem cells and their role in resistance to Endocrine Therapy"" Horm Canc.

Sabnis, G., O. Goloubeva, et al. (2010). "HDAC inhibitor entinostat restores responsiveness of letrozole resistant MCF-7Ca xenografts to AIs through modulation of Her-2." Mol Cancer Ther. 2013 Oct 3. [Epub ahead of print]

Sabnis, G., O. Goloubeva, et al. (2011). "Functional activation of the estrogen receptor-a and aromatase by the HDAC inhibitor entinostat sensitizes ER-negative tumors to letrozole." Cancer Res. Mar 1;71(5):1893-903. Epub 2011 Jan 18.

Shah, P., Gau, Y., Sabnis, G. (2013). " Histone deacetylase inhibitor entinostat reverses epithelial to mesenchymal transition of breast cancer cells by reversing the repression of E-cadherin." Breast Canc Res Treat

Srivastava, R., R. Kurzrock, et al. (2010). "MS-275 sensitizes TRAIL-resistant breast cancer cells, inhibits angiogenesis and metastasis, and reverses epithelial-mesenchymal transition In vivo." Mol Cancer Ther. 9(12):3254-66.

Thomas, S. and P.N. Munster. (2009). "Histone deacetylase inhibitor induced modulation of anti-estrogen therapy." Cancer Lett. 280:184-91.

Wardley, A.M., R. Stein, et al. (2010). "Phase II data for entinostat, a class 1 selective histone deacetylase inhibitor, in patients whose breast cancer is progressing on aromatase inhibitor therapy." JCO. 2010 ASCO annual meeting proceedings; 28(15)_suppl; 1052.

Yardley, D., R. Ismail-Khan, et al. (2013). "A randomized phase 2, double-blind, placebo-controlled study of exemestane with and without entinostat (SNDX-275) in postmenopausal women with locally recurrent or metastatic estrogen receptor-positive breast cancer progressing on treatment with a non-steroidal aromatase inhibitor." JCO

Entinostat / HDACi / Lymphoma / Leukemia

Ashraf, U., M.S. Czuczman, et al. (2009). "Entinostat (SNDX-275), a novel DAC inhibitor, is highly effective in rituximab-[chemotherapy]-sensitive or rituximab-[chemotherapy]-resistant lymphomas and has synergistic anti-tumor activity when combined with bortezomib." ASH Meeting Poster.

Buglio, D., G.V. Georgakis, et al. (2008). "Vorinostat inhibits STAT6-mediated TH2 cytokine and TARC production and induces cell death in Hodgkin lymphoma cell lines." Blood. 112(4):1424-33.

Frys, S., M. J. Barth, et al. (2012) "Entinostat, a novel histone deacetylase (HDACi) inhibitor enhances the anti-tumor activity of Bortezomib (BTZ) in rituximab-chemotherapy sensitive and resistant lymphoma cell lines." ASH 2012 poster.

Kashkhely, N., D. Buglio, et al. (2009). "The histone deacetylase (HDAC) inhibitor entinostat (SNDX-275) targets Hodgkin lymphoma through a dual mechanism of immune modulation and apoptosis induction." ASH Meeting Poster.

Ramsey, J. L. M. J. Kettyle, et. al. (2013) "Entinostat Prevents Leukemia Maintenance in a Collaborating Oncogene-Dependent Model of Cytogenetically Normal Acute Myeloid Leukemia." Stem Cells 2013(31):1434–1445.

Younes, A., F. Hernandez, et al. (2011). "The HDAC inhibitor entinostat (SNDX-275) induces clinical responses in patients with relapsed and refractory Hodgkin's lymphoma: results of ENGAGE-501 multicenter phase 2 study." ASH 2011 poster.

Younes, A., P.J. Rosen, et al. (2010). "ENGAGE-501: Phase II study investigating the role of epigenetic therapy with entinostat (SNDX-275) in relapsed and refractory Hodgkin's lymphoma (HL)." ASCO 2010 poster. J Clin Oncol 28: 15s, 210 (suppl; abstr TPS298).

Choudhary, C., C. Kumar, et al. (2009). "Lysine acetylation targets protein complexes and co-regulates major cellular functions." Sciencexpress. 1-16.

Entinostat / HDACi / Immunomodulation

Buglio, D., N. Kashkhely, et al. (2011). "HDAC11 plays an essential role in regulating OX40 ligand expression in Hodgkin lymphoma." Blood. Online.

Kim, K., Skora, A., et al. (2014). "Eradication of metastatic mouse cancers resistant to immune checkpoint blockade by suppression of myeloid-derived cells." PNAS. 2014 July 28. Online.

Pili, R., L. Shen, et al. (2013). "Phase I study of high-dose interleukin 2, aldesleukin, in combination with the histone deacetylase inhibitor, entinostat, in patients with metastatic renal cell carcinoma: Safety data." ASCO Genitourinary poster.

Shen, L., M. Ciesielksi, et al. (2012). "Class I histone deacetylase inhibitor entinostat suppresses regulatory T cells and enhances immunotherapies in renal and prostate cancer models." PLoSOne. 7(1):1-14.

Entinostat

Abraham, J., Nunez-Alvarez, Y., et al. (2014) "Lineage of origin in rhabdomyosarcoma informs pharmacological response." Genes Dev. 28:1578-1591.

Choudhary, C., C. Kumar, et al. (2009). "Lysine acetylation targets protein complexes and co-regulates major cellular functions." SciencExpress. 1-16.

Chung, E.J., S. Lee, et al. (2005). "Histone deacetylase inhibitor pharmacodynamic analysis by multiparameter flow cytometry." Annals Clin Lab Science. 35(4):397-405.

Gojo, I., A. Jiemjit, et al. (2007) "Phase 1 and pharmacologic study of MS-275, a histone deacetylase inhibitor, in adults with refractory and relapsed acute leukemias." Blood. 109(7):2781-90.

Gore, L., M. Rothenberg, et al. (2008). "A phase I and pharmacokinetic study of the oral histone deacetylase inhibitor, MS-275, in patients with refractory solid tumors and lymphomas." Clin Cancer Res. 14(14):4517-25.

Hauschild, A., U. Trefzer, et al. (2008). "Multicenter phase II trial of the histone deacetylase inhibitor pyridylmethyl-N-{4-[(2-aminophenyl)-carbamoyl]-benzyl}-carbamate in pretreated metastatic melanoma." Melanoma Res. 18(4):274-78.

Hess-Stumpp, H., T.U. Bracker, et al. (2007). "MS-275, a potent orally available inhibitor of histone deacetylases--the development of an anticancer agent." Int J Biochem Cell Biol. 39(7-8):1388-405.

Kummar, S., M. Gutierrez, et al. (2007). "Phase I trial of MS-275, a histone deacetylase inhibitor, administered weekly in refractory solid tumors and lymphoid malignancies." Clin Cancer Res 13(18):5411-17.

Ryan, Q.C., D. Headlee, et al. (2005). "Phase I and pharmacokinetic study of MS-275, a histone deacetylase inhibitor, in patients with advanced and refractory solid tumors or lymphoma." J Clin Oncol. 23(17):3912–22.