Targeting androgen receptor-independent pathways in therapy-resistant prostate cancer

doi:10.1016/j.ajur.2018.11.002

Asian Journal of Urology, 2019, 6 (1): 91-98 doi: 10.1016/j.ajur.2018.11.002

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Targeting androgen receptor-independent pathways in therapy-resistant prostate cancer

Lingfan Xu^a,b,Junyi Chen^c,Weipeng Liu^d,Chaozhao Liang^a,Hailiang Hu^b,Jiaoti Huang^b,*(

)

a Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
b Department of Pathology, Duke University School of Medicine, Durham, NC, USA
c Department of Urology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
d Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, China

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Abstract

Since androgen receptor (AR) signaling is critically required for the development of prostate cancer (PCa), targeting AR axis has been the standard treatment of choice for advanced and metastatic PCa. Unfortunately, although the tumor initially responds to the therapy, treatment resistance eventually develops and the disease will progress. It is therefore imperative to identify the mechanisms of therapeutic resistance and novel molecular targets that are independent of AR signaling. Recent advances in pathology, molecular biology, genetics and genomics research have revealed novel AR-independent pathways that contribute to PCa carcinogenesis and progression. They include neuroendocrine differentiation, cell metabolism, DNA damage repair pathways and immune-mediated mechanisms. The development of novel agents targeting the non-AR mechanisms holds great promise to treat PCa that does not respond to AR-targeted therapies.

Key words： Prostate cancer Therapeutic resistance Androgen receptor Neuroendocrine Cancer metabolism DNA damage repair

Received: 06 September 2018 Available online: 28 November 2018

Corresponding Authors: Jiaoti Huang E-mail: jiaoti.huang@duke.edu

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Lingfan Xu,Junyi Chen,Weipeng Liu, et al. Targeting androgen receptor-independent pathways in therapy-resistant prostate cancer[J]. Asian Journal of Urology, 2019, 6(1): 91-98.

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