Prostate cancer therapies and fertility: What do we really know?

The nuclear receptor superfamily comprises a large group of proteins with functions essential for cell signaling, survival, and proliferation. There are multiple distinctions between nuclear superfamily classes defined by hallmark differences in function, ligand binding, tissue specificity, and DNA binding. In this review, we utilize the initial classification system, which defines subfamilies based on structure and functional difference. The defining feature of the nuclear receptor superfamily is that these proteins function as transcription factors. The loss of transcriptional regulation or gain of functioning of these receptors is a hallmark in numerous diseases. For example, in prostate cancer, the androgen receptor is a primary target for current prostate cancer therapies. Targeted cancer therapies for nuclear hormone receptors have been more feasible to develop than others due to the ligand availability and cell permeability of hormones. To better target these receptors, it is critical to understand their structural and functional regulation. Given that late-stage cancers often develop hormone insensitivity, we will explore the strengths and pitfalls of targeting other transcription factors outside of the nuclear receptor superfamily such as the signal transducer and activator of transcription (STAT).

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Abstract 674: ODM-201 - New generation androgen receptor inhibitor targeting resistance mechanisms to androgen signalling-directed prostate cancer therapies

10.1158/1538-7445.am2014-674 ◽

2014 ◽

Author(s):

Anu-Maarit Moilanen ◽

Reetta Riikonen ◽

Pekka J. Kallio

Keyword(s):

Prostate Cancer ◽

Androgen Receptor ◽

Resistance Mechanisms ◽

Cancer Therapies ◽

New Generation ◽

Receptor Inhibitor

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A Case of Leptomeningeal Carcinomatosis from Aggressive Metastatic Prostate Cancer

Case Reports in Oncology ◽

10.1159/000499761 ◽

2019 ◽

Vol 12 (1) ◽

pp. 311-316 ◽

Cited By ~ 1

Author(s):

Ryan David Carroll ◽

E. Cindy Leigh ◽

Zachary Curtis ◽

Anthony Thorpe ◽

Jason Ballengee ◽

...

Keyword(s):

Prostate Cancer ◽

Treatment Options ◽

Brain Mri ◽

Altered Mental Status ◽

Leptomeningeal Carcinomatosis ◽

Cancer Therapies ◽

Csf Cytology ◽

Lower Extremity Weakness ◽

Confirmatory Tests ◽

Technological Improvements

Leptomeningeal carcinomatosis (LC) is a rare leptomeningeal spread of diffusely metastatic tumors. It occurs more commonly with hematologic tumors, less commonly with solid tumors, and is exceedingly rare in prostate cancer. Due to its scarcity, it has traditionally been difficult to diagnose LC but advancement of MRI has helped considerably. However, even with technological improvements, pre-mortem diagnosis of LC remains difficult and controversial. Our case is a 71-year-old male with prostate cancer with bone metastases who presented to our facility with altered mental status (AMS), lower extremity weakness, and worsening diarrhea. The diarrhea was responsive to antibiotic therapy, but his AMS did not resolve. A head CT without contrast was negative but follow-up brain MRI revealed leptomeningeal enhancement highly suggestive of LC. Cerebrospinal fluid (CSF) cytology results were negative and other CSF studies were inconclusive. Although further studies were planned, the patient continued to deteriorate, and the family elected to withdraw care. He passed away without beginning treatment for the LC. Despite advances in cancer therapies, LC remains difficult to diagnose and treat. Imaging may be suggestive of the condition but the confirmatory tests such as repeated CSF cytology or meningeal biopsy are not only invasive but also usually occur postmortem. Additional methods of CSF testing have been studied to evaluate their role in accurately diagnosing LC but low specificity for LC has somewhat limited their use. Although treatment options are mainly palliative in nature, prompt recognition and early treatment could grant valuable time for patients and families.

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p53 status implicated in IGF-1-targeting prostate cancer therapies

Expert Review of Anticancer Therapy ◽

10.1586/14737140.8.6.849 ◽

2008 ◽

Vol 8 (6) ◽

pp. 849-851

Keyword(s):

Prostate Cancer ◽

Cancer Therapies ◽

P53 Status

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PCN21: DIFFERENCES IN HUSBAND/WIFE PREFERENCES AND UTILITIES FOR PROSTATE CANCER THERAPIES

Value in Health ◽

10.1016/s1098-3015(10)63941-1 ◽

2003 ◽

Vol 6 (3) ◽

pp. 235-236

Author(s):

DW Bruner ◽

A Hanlon ◽

S Kulkarni ◽

S Mazzoni ◽

S Linton ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Therapies

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SHORT-TERM OUTCOMES FOLLOWING ORAL HORMONAL PROSTATE CANCER THERAPIES BY PRE-EXISTING CARDIOVASCULAR CONDITIONS: A POPULATION-BASED STUDY

Journal of Geriatric Oncology ◽

10.1016/s1879-4068(19)31238-x ◽

2019 ◽

Vol 10 (6) ◽

pp. S72

Author(s):

G.Lu Yao ◽

N. Nikita ◽

S.W. Keith ◽

G. Nightingale ◽

K. Gandhi ◽

...

Keyword(s):

Prostate Cancer ◽

Population Based ◽

Cancer Therapies ◽

Short Term ◽

Population Based Study

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Prostate epithelial cell differentiation and its relevance to the understanding of prostate cancer therapies

Clinical Science ◽

10.1042/cs20040241 ◽

2004 ◽

Vol 108 (1) ◽

pp. 1-11 ◽

Cited By ~ 48

Author(s):

Ronan M. LONG ◽

Colm MORRISSEY ◽

John M. FITZPATRICK ◽

R. William G. WATSON

Keyword(s):

Prostate Cancer ◽

Epithelial Cells ◽

Prostate Gland ◽

Western World ◽

Cancer Therapies ◽

Normal Prostate ◽

Full Characterization ◽

Prostate Epithelial Cells ◽

Common Malignancy

Prostate cancer is the most common malignancy in males in the western world. However, little is known about its origin and development. This review highlights the biology of the normal prostate gland and the differentiation of basal epithelial cells to a secretory phenotype. Alterations in this differentiation process leading to cancer and androgen-independent disease are discussed, as well as a full characterization of prostate epithelial cells. A full understanding of the origin and characteristics of prostate cancer epithelial cells will be important if we are to develop therapeutic strategies to combat the heterogeneous nature of this disease.

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Overall survival (OS) of African-American (AA) and Caucasian (CAU) men who received sipuleucel-T for metastatic castration-resistant prostate cancer (mCRPC): Final PROCEED analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.5035 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 5035-5035 ◽

Cited By ~ 2

Author(s):

A. Oliver Sartor ◽

Andrew J. Armstrong ◽

Chiledum Ahaghotu ◽

David G. McLeod ◽

Matthew R. Cooperberg ◽

...

Keyword(s):

Prostate Cancer ◽

Specific Antigen ◽

Prostate Cancer Risk ◽

Sensitivity Analyses ◽

Number Needed To Treat ◽

Cancer Therapies ◽

Matched Cohort ◽

Castration Resistant Prostate Cancer ◽

Multivariable Analyses ◽

Baseline Psa

5035 Background: Prostate cancer risk and mortality are higher in AAs versus CAUs. Post-hoc analyses of pooled Phase 3 data (n = 737) suggested substantial OS benefit for AA men receiving sipuleucel-T (n = 33) vs placebo (n = 10) (McLeod 2012). Compared with pooled placebo patients (n = 249), number needed to treat for OS benefit at 3 years was 3 for AAs and 8 for all sipuleucel-T-treated patients (n = 488) (Moses 2019). Herein we analyzed PROCEED (NCT01306890), a large real-world registry, in which all patients received sipuleucel-T. Methods: In PROCEED, 1902 mCRPC patients received ≥1 sipuleucel-T infusion. OS of all AA (n = 221) and CAU (n = 1649) men were compared. Baseline prostate-specific antigen (PSA), the most important prognostic variable for OS after sipuleucel-T (Schellhammer 2013), substantially differed by race. Thus, OS for a PSA-matched cohort (n = 219 AA; n = 438 CAU) was compared and univariable/multivariable analyses were performed. Post-sipuleucel-T use of OS-prolonging anticancer interventions was also assessed. Results: After a median follow-up of 46.6 mo, median OS was 35.2 (all sipuleucel-T-treated AAs) and 29.9 mo (all sipuleucel-T-treated CAUs): HR 0.81, 95% CI 0.68–0.97; P = 0.03. In the PSA-matched cohort, median OS was 35.3 and 25.8 mo, respectively (HR 0.70, 95% CI 0.57–0.86; P < 0.001). Sipuleucel-T-treated AAs with lower baseline PSA had markedly longer median OS vs sipuleucel-T-treated CAUs. Among those with ≤ median baseline PSA (29.48 ng/ml), median OS was 54.3 mo (AA) vs. 33.4 (CAUs); HR 0.52, 95% CI 0.37–0.72; p < 0.001. Along with other known prognostic factors, AA race was independently associated with prolonged OS on detailed multivariable analyses (HR 0.60, 95% CI 0.48–0.74; p < 0.001) and confirmed on sensitivity analyses. Post-sipuleucel-T life-prolonging anti-cancer therapies were balanced between groups. Conclusions: Sipuleucel-T-treated AAs had significantly improved OS vs sipuleucel-T-treated CAUs. This analysis marks the largest known racial difference in OS in response to any therapy for mCRPC, a finding with implications for both prostate cancer pathophysiology and cancer immunotherapy. Clinical trial information: NCT01306890.

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