Scott M. Dehm, PhD, University Minnesota, Twin Cities

Scott M. Dehm, PhD

The Dehm research laboratory focuses on the role of the androgen receptor (AR) and alterations in AR signaling in prostate cancer development and progression. As they develop, nearly all metastatic prostate cancers remain dependent on androgens--male hormones of which testosterone is best known. Following treatment targeting the AR including anti-androgen drug therapies and surgical castration to prevent androgen production, patients typically develop resistance. Dehm studies the changes that occur in the AR in response to these drug therapies to understand the mechanisms underlying the progression to therapy-resistant disease. His work has revealed new ways in which cancer cells can re-activate the androgen/AR pathway. If these mechanisms are better understood, new AR-targeted therapies could be developed that suppress prostate cancer growth more effectively with more durable remissions.

 

 

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References

  1. Li Y, Alsagabi M, Fan D, Bova GS, Tewfik AH, Dehm SM. Intragenic rearrangement and altered RNA splicing of the androgen receptor in a cell-based model of prostate cancer progression. Cancer Res. 2011;71(6):2108ñ2117. doi:10.1158/0008-5472.CAN-10-1998.
  2. Nyquist MD, Li Y, Hwang TH, et al. TALEN-engineered AR gene rearrangements reveal endocrine uncoupling of androgen receptor in prostate cancer. Proc Natl Acad Sci U S A. 2013;110(43):17492ñ17497. doi:10.1073/pnas.1308587110.
  3. Chan SC, Selth LA, Li Y, et al. Targeting chromatin binding regulation of constitutively active AR variants to overcome prostate cancer resistance to endocrine-based therapies. Nucleic Acids Res. 2015;43(12):5880ñ5897. doi:10.1093/nar/gkv262.
  4. Dalal K, Che M, Que NS, et al. Bypassing Drug Resistance Mechanisms of Prostate Cancer with Small Molecules that Target Androgen Receptor-Chromatin Interactions. Mol Cancer Ther. 2017;16(10):2281ñ2291. doi:10.1158/1535-7163.MCT-17-0259.
  5. Yin Y1, Li R2, Xu K, Ding S2,, Li J2, Baek G, Ramanand SG5, Ding S, Liu Z2,, Gao Y, Kanchwala MS6, Li X, Hutchinson R, Liu X, Woldu SL, Xing C6, Desai NB, Feng FY, Burma S, de Bono JS, Dehm SM, Mani RS, Chen BPC, Raj GV. Androgen Receptor Variants Mediate DNA Repair after Prostate Cancer Irradiation. Cancer Res. 2017 Sep 15;77(18):4745-4754. doi: 10.1158/0008-5472.CAN-17-0164. Epub 2017 Jul 28.
  6. Van Etten JL, Nyquist M, Li Y, et al. Targeting a Single Alternative Polyadenylation Site Coordinately Blocks Expression of Androgen Receptor mRNA Splice Variants in Prostate Cancer. Cancer Res. 2017;77(19):5228ñ5235. doi:10.1158/0008-5472.CAN-17-0320.