MP64-15 PRO-INFLAMMATORY CYTOKINE GENES ARE DRIVERS OF PROSTATE CANCER PROGRESSION AND CASTRATE RESISTANT PROSTATE CANCER

While androgen-targeted therapies are routinely used in advanced prostate cancer (PCa), their effect is poorly understood in treating bone metastatic lesions and ultimately results in the development of metastatic castrate resistant prostate cancer (mCRPC). Here, we used an all-human microtissue-engineered model of mineralized metastatic tissue combining human osteoprogenitor cells, 3D printing and prostate cancer cells, to assess the effects of the antiandrogens, bicalutamide, and enzalutamide in this microenvironment. We demonstrate that cancer/bone stroma interactions and antiandrogens drive cancer progression in a mineralized microenvironment. Probing the bone microenvironment with enzalutamide led to stronger cancer cell adaptive responses and osteomimicry than bicalutamide. Enzalutamide presented with better treatment response, in line with enzalutamide delaying time to bone-related events and enzalutamide extending survival in mCRPC. The all-human microtissue-engineered model of mineralized metastatic tissue presented here represents a substantial advance to dissect the role of the bone tumor microenvironment and responses to therapies for mCPRC.

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613 IMMEDIATE, COMPARED TO DEFERRED, COMBINED ANDROGEN BLOCKADE PROLONGS TIME TO CASTRATE-RESISTANT LNCAP PROSTATE CANCER PROGRESSION IN VIVO

The Journal of Urology ◽

10.1016/j.juro.2011.02.1466 ◽

2011 ◽

Vol 185 (4S) ◽

Author(s):

Hidetoshi Kuruma ◽

Kilian Gust ◽

Hiroaki Matsumoto ◽

Amina Zoubeidi ◽

Chirstian Thomas ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Progression ◽

Prostate Cancer Progression ◽

Combined Androgen Blockade ◽

Castrate Resistant ◽

Androgen Blockade

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The Interactions between Insulin and Androgens in Progression to Castrate-Resistant Prostate Cancer

Advances in Urology ◽

10.1155/2012/248607 ◽

2012 ◽

Vol 2012 ◽

pp. 1-11 ◽

Cited By ~ 13

Author(s):

Jennifer H. Gunter ◽

Amy A. Lubik ◽

Ian McKenzie ◽

Michael Pollak ◽

Colleen C. Nelson

Keyword(s):

Prostate Cancer ◽

Metabolic Syndrome ◽

Cancer Progression ◽

Tumour Regression ◽

Rapid Progression ◽

Testosterone Levels ◽

Resistant Disease ◽

The Metabolic Syndrome ◽

Castrate Resistant Prostate Cancer ◽

Castrate Resistant

An association between the metabolic syndrome and reduced testosterone levels has been identified, and a specific inverse relationship between insulin and testosterone levels suggests that an important metabolic crosstalk exists between these two hormonal axes; however, the mechanisms by which insulin and androgens may be reciprocally regulated are not well described. Androgen-dependant gene pathways regulate the growth and maintenance of both normal and malignant prostate tissue, and androgen-deprivation therapy (ADT) in patients exploits this dependence when used to treat recurrent and metastatic prostate cancer resulting in tumour regression. A major systemic side effect of ADT includes induction of key features of the metabolic syndrome and the consistent feature of hyperinsulinaemia. Recent studies have specifically identified a correlation between elevated insulin and high-grade PCa and more rapid progression to castrate resistant disease. This paper examines the relationship between insulin and androgens in the context of prostate cancer progression. Prostate cancer patients present a promising cohort for the exploration of insulin stabilising agents as adjunct treatments for hormone deprivation or enhancers of chemosensitivity for treatment of advanced prostate cancer.

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Roles of the HOXA10 gene during castrate-resistant prostate cancer progression

Endocrine Related Cancer ◽

10.1530/erc-18-0465 ◽

2019 ◽

Vol 26 (3) ◽

pp. 279-292 ◽

Cited By ~ 2

Author(s):

Zhi Long ◽

Yinan Li ◽

Yu Gan ◽

Dongyu Zhao ◽

Guangyu Wang ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Progression ◽

Fatty Acid Synthase ◽

Prostate Gland ◽

Gene Promoter ◽

Rna Seq ◽

Castrate Resistant Prostate Cancer ◽

Castrate Resistant ◽

Poor Patient Survival

Homeobox A10 (HOXA10) is an important transcription factor that regulates the development of the prostate gland. However, it remains unknown whether it modulates prostate cancer (PCa) progression into castrate-resistant stages. In this study, we have applied RNA in situ hybridization assays to demonstrate that downregulation of HOXA10 expression is associated with castrate-resistant PCa. These findings are supported by public RNA-seq data showing that reduced HOXA10 expression is correlated with poor patient survival. We show that HOXA10 suppresses PCa cell proliferation, anchorage colony formation and xenograft growth independent to androgens. Using AmpliSeq transcriptome sequencing, we have found that gene groups associated with lipid metabolism and androgen receptor (AR) signaling are enriched in the HOXA10 transcriptome. Furthermore, we demonstrate that HOXA10 suppresses the transcription of the fatty acid synthase (FASN) gene by forming a protein complex with AR and prevents AR recruitment to the FASN gene promoter. These results lead us to conclude that downregulation of HOXA10 gene expression may enhance lipogenesis to promote PCa cell growth and tumor progression to castrate-resistant stage.

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