Developmental Therapeutics; Multidisciplinary Breast Cancer Team
Research interests: Breast cancer, macroautophagy and antiestrogen resistance
In the 20 years since anti-estrogen drugs were introduced, they have proven themselves to be some of the most effective drugs available against breast cancer. Yet for some 30 to 40 percent of patients whose cancer becomes resistant, it is not enough.
The problem surfaced about 20 years ago, and laboratories around the country are working on intervention strategies. One culprit is macroautophagy, the focus of Dr. Patricia Schoenlein’s laboratory at MCG.
Anti-estrogen drugs bind estrodol, thus starving the estrogen-addicted tumor. Rather than starve, some cancer cells will self-digest, breaking down nutrients within the cell and recycling them. In time, the cancer reasserts itself.
Her strategy is to give the anti-estrogen drugs a longer time to work by teaming them with chloroquine — one of the oldest drugs for malaria. Chloroquine also has few side effects. The chloroquine works against malaria becasue it binds lysosone — the necessary component within a tumor cell that sets up macroautophagy.
At this early stage, her work has attracted significant funding from the National Institute of Health. Her hope is that by blocking macroautophagy, anti-estrogen therapies will do more than buy time for patients. They will rid the patient of breast cancer.
“If we understand how the tumor cells become resistant, then we feel like we could better design the therapy,” she says.
Dr. Schoenlein received a BS degree in 1978 from the University of South Carolina, followed by an MS in 1981 and a PhD in 1988, both also from USC. She has collaborated on 37 articles published in peer-reviewed professional journals.
- National Cancer Institute: “Antiestrogen-induced autophagy: a mechanism of cell survival in ER+ breast cancer” 2008 -2011, P. Schoenlein, PI
- National Cancer Institute: “Role of Epigenetic Repression of IRF8 in Tumor Progression/Metastasis” 2008-2013, (K Liu, PI)
Grant information is updated quarterly.
- Cancer Research
- Clinical Cancer Research
- Journal of Physiology
- Journal of Biological Chemistry
- Molecular Endocrinology
- Cell Division
Periyasamy-Thandavan S, Jackson WH, Samaddar JS, Erickson B, Barrett JR, Raney L, Gopal E, Ganapathy V, Hill WD, Bhalla KN, Schoenlein PV. Bortezomib blocks the catabolic process of autophagy via a cathepsin-dependent mechanism, affects endoplasmic reticulum stress and induces caspase-dependent cell death in antiestrogen-sensitive and resistant ER+ breast cancer cells. Autophagy. 2010 Jan;6(1):19-35.
Schoenlein PV, Periyasamy-Thandavan S, Samaddar JS, Jackson WH, Barrett JT. Autophagy facilitates the progression of ERalpha-positive breast cancer cells to antiestrogen resistance. Autophagy. 2009 Apr;5(3):400-3.
Yang D, Wang S, Brooks C, Dong Z, Schoenlein PV, Kumar V, Ouyang X, Xiong H, Lahat G, Hayes-Jordan A, Lazar A, Pollock R, Lev D, Liu K. IFN regulatory factor 8 sensitizes soft tissue sarcoma cells to death receptor-initiated apoptosis via repression of FLICE-like protein expression. Cancer Res. 2009 Feb 1;69(3):1080-8.
Samaddar JS, Gaddy VT, Duplantier J, Thandavan SP, Shah M, Smith MJ, Browning D, Rawson J, Smith SB, Barrett JT, Schoenlein PV. A role for macroautophagy in protection against 4-hydroxytamoxifen-induced cell death and the development of antiestrogen resistance. Mol Cancer Ther. 2008 Sep;7(9):2977-87.
Kwon IK, Schoenlein PV, Delk J, Liu K, Thangaraju M, Dulin NO, Ganapathy V, Berger FG, Browning DD. Expression of cyclic guanosine monophosphate-dependent protein kinase in metastatic colon carcinoma cells blocks tumor angiogenesis. Cancer. 2008 Apr 1;112(7):1462-70.
Publications are updated quarterly. For a complete listing, see Dr. Schoenlein’s work on PubMed.
- Associate Professor, Surgery, Radiology, Cellular Biology and Anatomy, College of Graduate Studies, Georgia Regents University
- Member, NIH study section Basic Mechanisms of Cancer Therapeutics
- Member, California Breast Cancer Research Program (CBCRP) Pathogenesis