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Photo of Debra A. Tonetti

Debra A. Tonetti

Professor of Pharmacology, Interim Department Head, Biopharmaceutical Sciences

Contact Information

833 South Wood Street; Room 451 (865)
Chicago, IL 60612

Phone: (312) 413-1169

Fax: (312) 996-1698


  • PhD, Loyola University Chicago, 1990

Research Interests

Pharmacology and biology of breast cancer including mechanisms of endocrine-resistance including protein kinase C (PKC) signaling as a mechanism of tamoxifen-resistant breast cancer; Breast cancer and lung cancer Patient-Derived Xenografts (PDXs); Development of the Selective human Estrogen Receptor Agonists (ShERPAs) TTC-352 in Phase I Clinical Trial for metastatic breast cancer

Intellectual Contributions

Journal Article

  • Pham TN, Perez-White BE, Zhao H, Mortazavi F, Tonetti D, . "Protein Kinase C Alpha enhances breast cancer cell migration through FOXC2-mediated repression of p120-catenin". BMC Cancer. 2017;17(832):13. doi:
  • Xiong R, Zhao J, Gutgesell LM, Wang Y, Lee SH, Karumudi B, Zhao H, Lu Y, Tonetti D, Thatcher GR. "Novel Selective Estrogen Receptor Downregulators (SERDs) Developed against Treatment-Resistant Breast Cancer.". Journal of medicinal chemistry. 2017;60(4):1325-1342. doi:10.1021/acs.jmedchem.6b01355.
  • Pham TT, Tonetti TA. "The role of protein kinase C alpha (PKCα) in breast cancer: A focus on endocrine resistant and triple negative subtype". Journal of Cancer Biology & Research. 2016;4(1):1076.
  • Xiong R, Patel H, Gutgesell LM, Zhao J, Delgado-Rivera L, Pham TN, Zhao H, Carlson K, Martin T, Katzenellenbogen JA, Moore T, Tonetti D, Thatcher GR. "Selective Human Estrogen Receptor Partial Agonists (ShERPAs) for Tamoxifen-Resistant Breast Cancer.". Journal of medicinal chemistry. 2015;. doi:10.1021/acs.jmedchem.5b01276.
  • Rauscher GH, Kresovich JK, Poulin M, Yan L, Macias V, Mahmoud AM, Al-Alem U, Kajdacsy-Balla A, Wiley EL, Tonetti D, Ehrlich M. "Exploring DNA methylation changes in promoter, intragenic, and intergenic regions as early and late events in breast cancer formation.". BMC cancer. 2015;15:816. doi:10.1186/s12885-015-1777-9.
  • Asztalos S, Pham TN, Gann PH, Hayes MK, Deaton R, Wiley EL, Emmadi R, Kajdacsy-Balla A, Banerji N, McDonald W, Khan SA, Tonetti D. "High incidence of triple negative breast cancers following pregnancy and an associated gene expression signature.". SpringerPlus. 2015;4:710. doi:10.1186/s40064-015-1512-7.
  • Weiss MS, Peñalver Bernabé B, Shin S, Asztalos S, Dubbury SJ, Mui MD, Bellis AD, Bluver D, Tonetti D, Saez-Rodriguez J, Broadbelt LJ, Jeruss JS, Shea LD. "Dynamic transcription factor activity and networks during ErbB2 breast oncogenesis and targeted therapy.". Integrative biology : quantitative biosciences from nano to macro. 2014;6(12):1170-82. doi:10.1039/c4ib00086b.
  • Stanford JC, Young C, Hicks D, Owens P, Williams A, Vaught DB, Morrison MM, Lim J, Williams M, Brantley-Sieders DM, Balko JM, Tonetti D, Earp, 3rd HS, Cook RS. "Efferocytosis produces a prometastatic landscape during postpartum mammary gland involution.". The Journal of clinical investigation. 2014;124(11):4737-52. doi:10.1172/JCI76375.
  • Molloy ME, White BE, Gherezghiher T, Michalsen BT, Xiong R, Patel H, Zhao H, Maximov PY, Jordan VC, Thatcher GR, Tonetti D. "Novel selective estrogen mimics for the treatment of tamoxifen-resistant breast cancer.". Molecular cancer therapeutics. 2014;13(11):2515-26. doi:10.1158/1535-7163.MCT-14-0319.
  • Peng M, Emmadi R, Wang Z, Wiley EL, Gann PH, Khan SA, Banerji N, McDonald W, Asztalos S, Pham TN, Tonetti D, Tyner AL. "PTK6/BRK is expressed in the normal mammary gland and activated at the plasma membrane in breast tumors.". Oncotarget. 2014;5(15):6038-48.
  • Zheng Y, Wang Z, Bie W, Brauer PM, Perez White BE, Li J, Nogueira V, Raychaudhuri P, Hay N, Tonetti D, Macias V, Kajdacsy-Balla A, Tyner AL. "PTK6 activation at the membrane regulates epithelial-mesenchymal transition in prostate cancer.". Cancer research. 2013;73(17):5426-37. doi:10.1158/0008-5472.CAN-13-0443.
  • Yun J, Pannuti A, Espinoza I, Zhu H, Hicks C, Zhu X, Caskey M, Rizzo P, D'Souza G, Backus K, Denning MF, Coon J, Sun M, Bresnick EH, Osipo C, Wu J, Strack PR, Tonetti D, Miele L. "Crosstalk between PKCα and Notch-4 in endocrine-resistant breast cancer cells.". Oncogenesis. 2013;2:e60. doi:10.1038/oncsis.2013.26.
  • Perez White B, Molloy ME, Zhao H, Zhang Y, Tonetti D. "Extranuclear ERα is associated with regression of T47D PKCα-overexpressing, tamoxifen-resistant breast cancer.". Molecular cancer. 2013;12:34. doi:10.1186/1476-4598-12-34.
  • Tonetti D, Gao W, Escarzaga D, Walters K, Szafran A, Coon JS. "PKCα and ERβ Are Associated with Triple-Negative Breast Cancers in African American and Caucasian Patients.". International journal of breast cancer. 2012;2012:740353. doi:10.1155/2012/740353.
  • Asztalos S, Gann PH, Hayes MK, Nonn L, Beam CA, Dai Y, Wiley EL, Tonetti D. "Gene expression patterns in the human breast after pregnancy.". Cancer prevention research (Philadelphia, Pa.). 2010;3(3):301-11. doi:10.1158/1940-6207.CAPR-09-0069.
  • Kim HY, Sohn J, Wijewickrama GT, Edirisinghe P, Gherezghiher T, Hemachandra M, Lu PY, Chandrasena RE, Molloy ME, Tonetti D, Thatcher GR. "Click synthesis of estradiol-cyclodextrin conjugates as cell compartment selective estrogens.". Bioorganic & medicinal chemistry. 2010;18(2):809-21. doi:10.1016/j.bmc.2009.11.046.
  • Zhang Y, Zhao H, Asztalos S, Chisamore M, Sitabkhan Y, Tonetti D. "Estradiol-induced regression in T47D:A18/PKCalpha tumors requires the estrogen receptor and interaction with the extracellular matrix.". Molecular cancer research : MCR. 2009;7(4):498-510. doi:10.1158/1541-7786.MCR-08-0415.
  • Rizzo P, Miao H, D'Souza G, Osipo C, Song LL, Yun J, Zhao H, Mascarenhas J, Wyatt D, Antico G, Hao L, Yao K, Rajan P, Hicks C, Siziopikou K, Selvaggi S, Bashir A, Bhandari D, Marchese A, Lendahl U, Qin JZ, Tonetti D, Albain K, Nickoloff BJ, Miele L. "Cross-talk between notch and the estrogen receptor in breast cancer suggests novel therapeutic approaches.". Cancer research. 2008;68(13):5226-35. doi:10.1158/0008-5472.CAN-07-5744.
  • Tonetti D, Zhang Y, Zhao H, Lim SB, Constantinou AI. "The effect of the phytoestrogens genistein, daidzein, and equol on the growth of tamoxifen-resistant T47D/PKC alpha.". Nutrition and cancer. 2007;58(2):222-9. doi:10.1080/01635580701328545.
  • Lin X, Yu Y, Zhao H, Zhang Y, Manela J, Tonetti D. "Overexpression of PKCalpha is required to impart estradiol inhibition and tamoxifen-resistance in a T47D human breast cancer tumor model.". Carcinogenesis. 2006;27(8):1538-46. doi:10.1093/carcin/bgl002.
  • Constantinou AI, White B, Tonetti D, Yang Y, Liang W, Li W, van Breemen RB. "The soy isoflavone daidzein improves the capacity of tamoxifen to prevent mammary tumours.". European journal of cancer (Oxford, England : 1990). 2005;41(4):647-54. doi:10.1016/j.ejca.2004.12.005.
  • Ee PL, Kamalakaran S, Tonetti D, He X, Ross DD, Beck WT. "Identification of a novel estrogen response element in the breast cancer resistance protein (ABCG2) gene.". Cancer research. 2004;64(4):1247-51.
  • Ee PL, Kamalakaran S, Tonetti D, He X, Ross DD, Beck WT. "Identification of a novel estrogen response element in the breast cancer resistance protein (ABCG2) gene.". Cancer research. 2004;64(4):1247-51.
  • Tonetti D, Rubenstein R, DeLeon M, Zhao H, Pappas SG, Bentrem DJ, Chen B, Constantinou A, Craig Jordan V. "Stable transfection of an estrogen receptor beta cDNA isoform into MDA-MB-231 breast cancer cells.". The Journal of steroid biochemistry and molecular biology. 2003;87(1):47-55.
  • Liu X, Pisha E, Tonetti D, Yao D, Li Y, Yao J, Burdette JE, Bolton JL. "Antiestrogenic and DNA damaging effects induced by tamoxifen and toremifene metabolites.". Chemical research in toxicology. 2003;16(7):832-7. doi:10.1021/tx030004s.
  • Tonetti D, Morrow M, Kidwai N, Gupta A, Badve S. "Elevated protein kinase C alpha expression may be predictive of tamoxifen treatment failure.". British journal of cancer. 2003;88(9):1400-2. doi:10.1038/sj.bjc.6600923.
  • Chisamore MJ, Ahmed Y, Bentrem DJ, Jordan VC, Tonetti D. "Novel antitumor effect of estradiol in athymic mice injected with a T47D breast cancer cell line overexpressing protein kinase Calpha.". Clinical cancer research : an official journal of the American Association for Cancer Research. 2001;7(10):3156-65.
  • Fournier DB, Chisamore M, Lurain JR, Rademaker AW, Jordan VC, Tonetti D. "Protein kinase C alpha expression is inversely related to ER status in endometrial carcinoma: possible role in AP-1-mediated proliferation of ER-negative endometrial cancer.". Gynecologic oncology. 2001;81(3):366-72. doi:10.1006/gyno.2001.6164.
  • Tonetti D, Chisamore MJ, Grdina W, Schurz H, Jordan VC. "Stable transfection of protein kinase C alpha cDNA in hormone-dependent breast cancer cell lines.". British journal of cancer. 2000;83(6):782-91. doi:10.1054/bjoc.2000.1326.
  • Tonetti D, Jordan VC. "The estrogen receptor: a logical target for the prevention of breast cancer with antiestrogens.". Journal of mammary gland biology and neoplasia. 1999;4(4):401-13.
  • Schafer JI, Liu H, Tonetti D, Jordan VC. "The interaction of raloxifene and the active metabolite of the antiestrogen EM-800 (SC 5705) with the human estrogen receptor.". Cancer research. 1999;59(17):4308-13.
  • Levenson AS, Tonetti D, Jordan VC. "The oestrogen-like effect of 4-hydroxytamoxifen on induction of transforming growth factor alpha mRNA in MDA-MB-231 breast cancer cells stably expressing the oestrogen receptor.". British journal of cancer. 1998;77(11):1812-9.
  • Tonetti D, O'Regan R, Tanjore S, England G, Jordan VC. "Antiestrogen stimulated human endometrial cancer growth: laboratory and clinical considerations.". The Journal of steroid biochemistry and molecular biology. 1998;65(1-6):181-9.
  • Tonetti D, Jordan VC. "The role of estrogen receptor mutations in tamoxifen-stimulated breast cancer.". The Journal of steroid biochemistry and molecular biology. 1997;62(2-3):119-28.
  • Jordan VC, MacGregor JI, Tonetti D. "Tamoxifen: from breast cancer therapy to the design of a postmenopausal prevention maintenance therapy.". Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 1997;7 Suppl 1:S52-7.
  • Jordan VC, MacGregor JI, Tonetti D. "Tamoxifen: from breast cancer therapy to the design of a postmenopausal prevention maintenance therapy.". Clinical oncology (Royal College of Radiologists (Great Britain)). 1997;9(6):390-4.
  • Tonetti D, Jordan VC. "Targeted antiestrogens.". Progress in clinical and biological research. 1997;396:245-55.
  • Tonetti D, Jordan VC. "Design of an ideal hormone replacement therapy for women.". Molecular carcinogenesis. 1996;17(3):108-11. doi:10.1002/(SICI)1098-2744(199611)17:3<108::AID-MC1>3.0.CO;2-B.
  • Tonetti D, Jordan VC. "Targeted anti-estrogens to treat and prevent diseases in women.". Molecular medicine today. 1996;2(5):218-23.
  • Tonetti D, Jordan VC. "Possible mechanisms in the emergence of tamoxifen-resistant breast cancer.". Anti-cancer drugs. 1995;6(4):498-507.
  • Tonetti D, Henning-Chubb C, Yamanishi DT, Huberman E. "Protein kinase C-beta is required for macrophage differentiation of human HL-60 leukemia cells.". The Journal of biological chemistry. 1994;269(37):23230-5.
  • Tonetti D, Horio M, Collart FR, Huberman E. "Protein kinase C beta gene expression is associated with susceptibility of human promyelocytic leukemia cells to phorbol ester-induced differentiation.". Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research. 1992;3(10):739-45.
  • Kelly GM, Druse MJ, Tonetti D, Oden BG. "Maternal ethanol consumption: binding of L-glutamate to synaptic membranes from whole brain, cortices, and cerebella of offspring.". Experimental neurology. 1986;91(2):219-28.
  • Druse MJ, Tonetti D, Smith, Jr DM. "Effects of maternal nutritional stress on synaptic plasma membrane proteins and glycoproteins in offspring.". Experimental neurology. 1982;78(1):99-111.


  • Halasi M, Zhao H, Dahari H, Bhat UG, Gonzalez EB, Lyubimo AV, Tonetti D, Gartel AL. (2010). "Thiazole antibiotics against breast cancer.". Cell cycle (Georgetown, Tex.). Vol. 9. Issue 6. Page(s) 1214-7.
  • Tonetti D. (2004). "Prevention of breast cancer by recapitulation of pregnancy hormone levels.". Breast cancer research : BCR. Vol. 6. Issue 1. Page(s) E8.

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