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Molecular Characterization of AR Ant...

Hertzog, Jennifer R.

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Molecular Characterization of AR Antagonist Resistance During Treatment of Prostate Cancer.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Molecular Characterization of AR Antagonist Resistance During Treatment of Prostate Cancer./
作者:	Hertzog, Jennifer R.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2021,
面頁冊數:	114 p.
附註:	Source: Dissertations Abstracts International, Volume: 82-05, Section: B.
Contained By:	Dissertations Abstracts International82-05B.
標題:	Cellular biology. -
電子資源:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28156175
ISBN:	9798691246968

Molecular Characterization of AR Antagonist Resistance During Treatment of Prostate Cancer.
Hertzog, Jennifer R.

Molecular Characterization of AR Antagonist Resistance During Treatment of Prostate Cancer. - Ann Arbor : ProQuest Dissertations & Theses, 2021 - 114 p.

Source: Dissertations Abstracts International, Volume: 82-05, Section: B.

Thesis (Ph.D.)--University of the Sciences in Philadelphia, 2021.

This item must not be sold to any third party vendors.

Prostate cancer is the most commonly diagnosed cancer in men and nearly 30,000 patients will die this year due to complications arising from the disease. Prostate cancer patients are frequently treated with androgen deprivation therapies, but the duration of response is variable, and patients frequently progress to an incurable stage of the disease referred to as castration-resistant prostate cancer (CRPC). Second-generation AR antagonists such as enzalutamide and apalutamide are effective therapies that block androgen receptor (AR) transactivation and signaling in over 50% of CRPC patients. However, an estimated 30% of responders will develop resistance to these therapies within two years. There is another class of AR antagonists which are referred to as pan AR antagonists, that have shown to inhibit the activity of wild-type AR as well as several mutated versions of AR. Currently, there are several pan AR antagonists in preclinical development and approved for the treatment of CRPC in patients harboring pathogenic point mutations in AR. We chose four genetically distinct AR-positive prostate cancer preclinical models to generate enzalutamide, JNJ-pan-AR, or apalutamide resistant cell lines. We then performed transcriptomic and proteomic profiling on the AR antagonist sensitive and resistant cell lines to uncover molecular alterations that may be critical to the maintenance and/ or predictive biomarkers of the resistant phenotype. Global profiling uncovered significant variability in molecular alterations across the AR antagonist resistant cell lines as well as the prostate cancer preclinical models. However, we uncovered upregulation of AKR1C3 protein expression across all three AR antagonist resistant cell lines using the LNCaP and LNCaP/AR preclinical models. Further characterization of the functional significance of AKR1C3 upregulation demonstrated that AKR1C3 protein expression contributes to JNJ-pan-AR resistance. Similar findings have reported the correlation between AKR1C3 expression and changes in drug efficacy across several chemotherapeutic agents approved to CRPC treatment. Collectively the findings from this study support the rationale of AKR1C3 as a target for AR antagonist resistant prostate cancer disease progression.

ISBN: 9798691246968Subjects--Topical Terms:

3172791
Cellular biology.
Subjects--Index Terms:

AR antagonists

Molecular Characterization of AR Antagonist Resistance During Treatment of Prostate Cancer.
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