Epithelial cancers share many properties with adult tissue-specific stem cells, including the capacities to proliferate, self-renew and differentiate. Recent work has indicated that adult tissue-specific stem cells are likely target cells for acquiring the initial mutations that lead to epithelial cancers (cells of origin). Dr. Andrew Goldstein’s lab is interested in 1) identifying stem and progenitor cells in the mouse and human genitourinary tract, 2) defining the unique mechanisms that progenitor cells utilize to survive, self-renew and generate cancer, and 3) interrogating the signaling pathways which can transform normal stem and progenitor cells.
Castration-resistant prostate cancer (CRPC) represents the advanced stage of the disease that recurs after androgen deprivation therapy. Few treatment options currently exist for men with CRPC. Goldstein’s lab is developing new in vivo models of CRPC initiated in naive benign primary human prostate cells isolated from patient specimens. Commonly mutated pathways and newly identified alterations are being investigated to determine the requirements to transform naive benign cells to primary prostate cancer and CRPC. Defining the alterations that drive advanced disease may provide an opportunity to predict response to hormonal therapy, and defining new pathways regulating disease progression may lead to new targeted therapies for the treatment of CRPC.
Selected Cancer-Related Publications:
Goldstein AS, Drake JM, Burnes DL, Finley DS, Zhang H, Reiter RE, Huang J, Witte ON. Purification and direct transformation of epithelial progenitor cells from primary human prostate. Nat Protoc. 2011 May;6(5):656-67. Epub 2011 Apr 21.
Goldstein AS, Huang J, Guo C, Garraway IP, Witte ON. Identification of a cell of origin for human prostate cancer. Science. 2010 Jul 30;329(5991):568-71.
Goldstein AS, Stoyanova T, Witte ON. Primitive origins of prostate cancer: in vivo evidence for prostate-regenerating cells and prostate cancer-initiating cells. Mol Oncol. 2010 Oct;4(5):385-96. Epub 2010 Jul 14.
Memarzadeh S, Zong Y, Janzen DM, Goldstein AS, Cheng D, Kurita T, Schafenacker AM, Huang J, Witte ON. Cell-autonomous activation of the PI3-kinase pathway initiates endometrial cancer from adult uterine epithelium. Proc Natl Acad Sci U S A. 2010 Oct 5;107(40):17298-303. Epub 2010 Sep 20.
Zong Y, Xin L, Goldstein AS, Lawson DA, Teitell MA, Witte ON. ETS family transcription factors collaborate with alternative signaling pathways to induce carcinoma from adult murine prostate cells. Proc Natl Acad Sci U S A. 2009 Jul 28;106(30):12465-70. Epub 2009 Jul 10.