Beyond the Abstract - Nuclear hormone receptor signals as new therapeutic targets for urothelial carcinoma, by Hiroshi Miyamoto, MD, PhD

BERKELEY, CA (UroToday.com) - In this article we, for the first time, review the involvement of sex hormones such as androgens and estrogens, as well as other steroid hormones including progesterone, glucocorticoid, vitamin D, and retinoids, and their cognate receptors in bladder cancer.

{tortags,49760,1}There are a number of promising data indicating that steroid hormone receptors, especially the androgen receptor (AR), modulate bladder carcinogenesis as well as cancer progression, although underlying mechanisms need to be further investigated. Accordingly, hormonal therapy, such as androgen deprivation, a critical therapeutic option for prostate cancer, can be applied to bladder cancer.

The available data for estrogen receptor (ER) signals appear to be less convincing, and further preclinical studies assessing the efficacy of estrogen deprivation/replacement, which has been widely used for the treatment in breast cancer patients/postmenopausal women, should be pursued in bladder cancer as well.

Experimental strategies targeting nuclear hormone receptor signals alone, or those combined with potentially relevant pathways, predominantly tested in other cancers, can also be investigated in bladder cancer. Potential clinical use of hormonal manipulation in bladder cancer includes prevention of superficial tumor recurrence and management of advanced tumor resistant to currently available aggressive treatment. Of note is that some bladder tumors likely lack a functional hormone receptor, and therefore, targeting each receptor pathway may not always be beneficial to every patient. For instance, future assessment of androgen deprivation therapy in bladder cancer should be limited to AR-positive tumors, in conjunction with focusing on identifying patients who will benefit from such treatment. Moreover, although current forms of hormone treatment are generally regarded as safe, caution should be exercised against its adverse effects.

In conclusion, current evidence described in this review article should be sufficient for bladder cancer to be a member of endocrine-related neoplasms. Nonetheless, the following issues remain unresolved in bladder cancer: 1) whether or not targeting nuclear hormone receptors really improves patient outcome; 2) how appropriate patients should be selected for each hormonal manipulation; and 3) optimal strategies of such hormonal treatment.

We hope to advance our understanding of the roles of respective hormones and their cognate receptors in human bladder cancer and to subsequently develop chemopreventive and/or therapeutic options via targeting these signaling pathways.

 

Written by:
Hiroshi Miyamoto, MD, PhD as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.

Nuclear hormone receptor signals as new therapeutic targets for urothelial carcinoma - Abstract

 

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