scholarly journals WOMEN IN CANCER THEMATIC REVIEW: New roles for nuclear receptors in prostate cancer

2016 ◽  
Vol 23 (11) ◽  
pp. T85-T108 ◽  
Author(s):  
Damien A Leach ◽  
Sue M Powell ◽  
Charlotte L Bevan
Keyword(s):  
Prostate Cancer ◽  
Nuclear Receptors ◽  
Nuclear Receptor ◽  
Current Knowledge ◽  
Transcriptional Responses ◽  
Number Variation ◽  
Genomic Studies ◽  
Life Threatening ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant

Prostate cancer has, for decades, been treated by inhibiting androgen signalling. This is effective in the majority of patients, but inevitably resistance develops and patients progress to life-threatening metastatic disease – hence the quest for new effective therapies for ‘castrate-resistant’ prostate cancer (CRPC). Studies into what pathways can drive tumour recurrence under these conditions has identified several other nuclear receptor signalling pathways as potential drivers or modulators of CRPC.The nuclear receptors constitute a large (48 members) superfamily of transcription factors sharing a common modular functional structure. Many of them are activated by the binding of small lipophilic molecules, making them potentially druggable. Even those for which no ligand exists or has yet been identified may be tractable to activity modulation by small molecules. Moreover, genomic studies have shown that in models of CRPC, other nuclear receptors can potentially drive similar transcriptional responses to the androgen receptor, while analysis of expression and sequencing databases shows disproportionately high mutation and copy number variation rates among the superfamily. Hence, the nuclear receptor superfamily is of intense interest in the drive to understand how prostate cancer recurs and how we may best treat such recurrent disease. This review aims to provide a snapshot of the current knowledge of the roles of different nuclear receptors in prostate cancer – a rapidly evolving field of research.

scholarly journals Genetics of Prostate Carcinoma

2021 ◽  
Vol 50 (1) ◽  
pp. 71
Author(s):  
Božo Krušlin ◽  
Lucija Škara ◽  
Tonći Vodopić ◽  
Borna Vrhovec ◽  
Jure Murgić ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Carcinoma ◽  
Poor Prognosis ◽  
Large Scale ◽  
Metastatic Prostate Cancer ◽  
Genetically Engineered ◽  
Genetically Engineered Mouse Models ◽  
Genomic Studies ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant

<p>The aim of this review is to provide a brief overview of some current approaches regarding diagnostics, pathologic features, treatment, and genetics of prostate carcinoma (PCa). Prostate carcinoma is the most common visceral tumor and the second most common cancer-related cause of death in males. Clinical outcomes for patients with localized prostate cancer are excellent, but despite advances in prostate cancer treatments, castrate-resistant prostate cancer and metastatic prostate cancer patients have a poor prognosis. Advanced large-scale genomic studies revealed a large number of genetic alterations in prostate cancer. The meaning of these alterations needs to be validated in the specific prostate cancer molecular subtype context. Along these lines, there is a critical need for establishing genetically engineered mouse models, which would include speckle type BTB/POZ protein and isocitrate Dehydrogenase (NADP (+)) 1 mutant, as well as androgen receptor neuroendocrine subtypes of prostate cancer. Another urgent need is developing highly metastatic prostate cancer models, as only up to 17% of available models dis- play bone metastases and exhibit a less typical neuroendocrine prostate cancer or sarcomatoid carcinoma. Moreover, androgen deprivation and relapse should be mimicked in the genetically engineered mouse models, as androgen independence may yield a better model for metastatic castrate-resistant prostate cancer. The development of such refined animal models should be guid- ed by comparative genomics of primary versus corresponding metastatic tumors. Such an approach will have the potential to illuminate the key genetic events associated with specific molecular prostate cancer subsets and indicate directions for effective therapy.</p><p><strong>Conclusion</strong>. Despite excellent results in the treatment of localized prostatic carcinoma, castrate-resistant prostate can- cer and metastatic prostate cancer have a poor prognosis. Advanced large-scale genomic studies revealed a large number of ge- netic alterations in PCa. Experimental models of prostate carcinoma in genetically modified mice could provide new data about the genetic changes in such cancers and help in developing better animal models for treatment resistant prostate carcinomas.</p>

Novel methodology for cost evaluation of anticancer drugs in castrate-resistant prostate cancer.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 200-200 ◽  
Author(s):  
Helmy M. Guirgis
Keyword(s):  
Quality Of Life ◽  
Prostate Cancer ◽  
Anticancer Drugs ◽  
Reference Value ◽  
Cost Evaluation ◽  
Life Threatening ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant ◽  
Fatal Adverse Events

200 Background: There is a need for a screening methodology to evaluate cost effectiveness of anticancer drugs. High costs raise concerns on approval, affordability and utilization. Objectives: Develop simplified methodology to screen and score cost versus value survival of docetaxel, cabazitaxel, abiraterone and sipuleucel-T in castrate- resistant prostate cancer (CRPC) Methods: Estimated costs in US $ of the entire course of an evaluated drug were added to downstream ancillary costs. The total was divided by the reported median survival gain over control in days. A reference value scale between 0- 100% was constructed with 0% assigned to cost/overall survival (OS) > $750, life threatening/ fatal adverse events (AEs) and worsened quality of life (QoL). A plan was designed to correct for AEs and QoL. Results were expressed as cost/OS and value and corrected scores. Results: Abiraterone at $5,000 per month x 6 months demonstrated cost/OS of $256 with 66% value and 61% corrected scores. Abiraterone x 9-12 months raised cost/OS and decreased scores. Generic docetaxel x 8 cycles demonstrated $63 cost/OS and 92% value score. Ancillary treatment increased cost/OS to $136 and decreased score to 82%. Cost/OS of cabazitaxel x 6 cycles ranged from $477- $596 with 21-36% scores. Corrections for AEs and QoL reduced scores to 6-21%. Sipuleucel-T demonstrated relatively higher cost/OS and lower scores. Conclusions: Preliminary findings would support utilization of docetaxel and abiraterone more than cabazitaxel and sipuleucel-T. The proposed methodology of cost versus value-survival could facilitate cost evaluation and budgetary planning of anticancer drugs.

Multi-parametric liquid biopsy analysis of circulating tumor cells (CTCs), cell-free DNA (cfDNA), and cell-free RNA (cfRNA) in metastatic castrate resistant prostate cancer (mCRPC).

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 274-274 ◽  
Author(s):  
Emmanuelle Hodara ◽  
Daniel Zainfeld ◽  
Gareth Morrison ◽  
Alexander Cunha ◽  
Yucheng Xu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Liquid Biopsy ◽  
Copy Number ◽  
Cell Capture ◽  
Multiple Cancer ◽  
Liquid Biopsies ◽  
Low Pass ◽  
Number Variation ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant

274 Background: Molecular profiling of prostate cancer using liquid biopsies such as CTC capture and cell-free nucleic acid analysis yield informative yet distinct datasets. Additional insights may be gained by simultaneously interrogating multiple liquid biopsy components to construct a more comprehensive molecular disease profile. We have conducted an initial proof of principle study aimed at piloting this multi-parametric approach. Methods: Blood was drawn under an IRB-approved protocol from 20 mCRPC patients. Samples were analyzed simultaneously for the following: CTC enumeration and single CTC and matched white blood cell capture for whole genome amplification and low-pass copy number variation; CTC DNA and matched cfDNA for somatic single nucleotide variant analysis; plasma cfRNA extraction and qRT-PCR for AR, AR-V7, and PCA3. When available, liquid biopsies were compared with matched tumor profiles. Results: Fifteen of 20 patients (75%) had detectable CTCs by CellSearch (range: 1-692/7.5mL, median: 16.5/7.5mL). Thirteen of 20 patients (65%) had detectable SSNVs in CTC DNA and/or matched cfDNA, including mutations in TP53, PIK3CA, HRAS, and EGFR. Matched CTC DNA and cfDNA demonstrated both shared and distinct SSNVs. Copy number analysis of single CTCs was performed in 2 patients, and both had CNVs in multiple cancer relevant genes. A majority of CNVs were present in matched solid tumor profiles, but some were exclusive to the liquid biopsies. Plasma PCA3 and AR transcripts were detected in 18/20 (90%) and AR-V7 in 4/20 (20%) cfRNA samples. Unique SSNVs were detected at second time points at disease progression (more are being collected). Conclusions: In this pilot cohort, simultaneous multi-parametric profiling was feasible for CTC DNA mutations and CNVs, and matched plasma cfDNA mutations and cfRNA gene expression. These disease-specific molecular profiles were often concordant with tumor tissues but also contained new, potentially actionable alterations unique to CTC DNA or cfDNA. Expanded studies will build upon this approach to optimally leverage liquid biopsies for molecularly directed patient management.

scholarly journals 225Actinium-labeled prostate-specific membrane antigen targeting peptide induces complete response in a metastatic prostate cancer patient

2021 ◽  
Vol 10 (5) ◽  
pp. 205846012110225
Author(s):  
Omer Aras ◽  
Stefan Harmsen ◽  
Richard Ting ◽  
Haluk B Sayman
Keyword(s):  
Prostate Cancer ◽  
Standard Of Care ◽  
Complete Response ◽  
Prostate Specific Membrane Antigen ◽  
Limited Data ◽  
Castrate Resistant Prostate Cancer ◽  
Targeting Peptide ◽  
Castrate Resistant ◽  
Specific Membrane

Targeted radionuclide therapy has emerged as a promising and potentially curative strategy for high-grade prostate cancer. However, limited data are available on efficacy, quality of life, and pretherapeutic biomarkers. Here, we highlight the case of a patient with prostate-specific membrane antigen (PSMA)-positive metastatic castrate-resistant prostate cancer who displayed complete response to 225Ac-PSMA-617 after having been resistant to standard-of-care therapy, then initially partially responsive but later resistant to subsequent immunotherapy, and resistant to successive 177Lu-PSMA-617. In addition, the patient’s baseline germline mutation likely predisposed him to more aggressive disease.

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