This laboratory is focused on androgen receptor (AR) function as it relates to prostate cancer. The first line of therapy for metastatic prostate cancer is androgen deprivation therapy (ADT). Almost all prostate cancers will express AR and require AR for survival, growth and disease progression, which is why the majority of patients initially respond well to ADT. However, metastatic disease eventually becomes resistant to ADT. Prostate cancer that progresses in the face of ADT is termed androgen-independent or castration-resistant prostate cancer (CRPC). Many laboratories have shown that AR is somehow reactivated by a gain-of-function in CRPC. Therefore, compounds that antagonize AR with novel mechanisms should be useful for the treatment of CRPC.
Specific goals of this laboratory are:
1) Elucidation of mechanisms of androgen receptor gain-of-function in prostate cancer that is resistant to ADT 2) Interrogation of androgen receptor transcriptional control 3) Devising novel methods of inhibiting androgen receptor transcription with synthetic chemist collaborators
RESEARCH INTERESTS
Prostate cancer
Androgen receptor
Androgen independence
Developmental therapeutics
RECENT PUBLICATIONS
Sharifi, N., "Hormonal Therapy for Prostate Cancer: Toward Further Unraveling of Androgen Receptor Function" Anticancer Agents Med Chem, [Epub ahead of print] December 2009
Sharifi, N., Hurt, E.M., Thomas, S.B. and Farrar, W.L., "Effects of Manganese Superoxide Dismutase Silencing on Androgen Receptor Function and Gene Regulation: Implications for Castration-Resistant Prostate Cancer" Clinical Cancer Research, 14(19):6073-80, October 2008
Sharifi, N., Hamada, A., Sissung, T., Danesi, R., Venzon, D., Gulley, J.L., Dahut, W.L., and Figg, W.D., "A polymorphism in a transporter of testosterone is a determinant of androgen independence in prostate cancer" BJU Int, 102(5):617-21, August 2008
Sharifi, N., Dahut, W.L., and Figg, W.D., "The genetics of castration-resistant prostate cancer: What can the germline tell us?" Clinical Cancer Research, 14(15):4691-3, August 2008
Sharifi, N., Figg, W.D. and Dahut, W.L., "Novel Therapies for Prostate Cancer" In: Gulley, J.L., Moul, J.W., Sandler, H.M. and Dahut, W.L. (Editors) Prostate Cancer Foundation Handbook. Lippincott William and Wilkins, In press
SIGNIFICANT PUBLICATIONS
Sharifi, N., Gulley, J. and Dahut, W.L., "Androgen deprivation therapy for prostate cancer" JAMA, 294:238-44, 2005
Sharifi, N., Hurt, E.M., Kawasaki, B.T and Farrar, W.L., "TGFBR3 loss and consequences in prostate cancer" Prostate, 67:301-11, 2007
Sharifi, N., Hamel, E., Lill, M., Prabhakar, R., Kane, C.T., Hossain, M.T., Jones, A., Dalton, J., and Farrar, W.L., "A bifunctional colchicinoid that binds to the androgen receptor" Molecular Cancer Therapeutics, 6:2328-37, 2007
Hamada, A., Sissung, T., Price, D.K., Danesi, R., Chau, C.H., Sharifi, N., et al., "A polymorphism in SLCO1B3 affects testosterone transport and is a determinant of clinical outcome in patients with prostate cancer" Clinical Cancer Research, 14(11):3312-8, June 2008
Sharifi, N., Hurt, E.M., and Farrar, W.L., "Androgen receptor expression in prostate cancer stem cells: is there a conundrum?" Cancer Chemotherapy and Pharmacology, 62(5):921-3, October 2008
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