Now showing 1 - 5 of 5
  • Publication
    Commercialized biomarkers: new horizons in prostate cancer diagnostics
    Limitations with current clinical tools available for diagnosis and prognosis of prostate cancer (PCa) have resulted in overdiagnosis and costly overtreatment, which is affecting the outcomes and quality of life of men. The biotech industry is investing significant resources into developing more specific biomarkers for PCa detection and patient stratification that would greatly advance the decision-making processes behind PCa management and treatment. In this review, we focus on those biomarkers that have been translated into commercial tests available to clinicians. Since these tests aim to fill specific gaps during the decision-making process of PCa management, we have grouped them based on the clinical question they claim to address, that is, improved PCa screening, false-negative biopsy dilemma, prognostic tests following a positive biopsy and tests predicting relapse/metastases after surgery. We evaluate each test with respect to its development, platform, clinical validation, biomatrix, regulatory approval status and cost.
      1077Scopus© Citations 12
  • Publication
    The analysis of serum response factor expression in bone and soft tissue prostate cancer metastases
    Castration-resistant prostate cancer (CRPC) represents a challenge to treat with no effective treatment options available. We recently identified serum response factor (SRF) as a key transcription factor in an in vitro model of castration resistance where we showed that SRF inhibition resulted in reduced cellular proliferation. We also demonstrated an association between SRF protein expression and CRPC in a cohort of castrate-resistant transurethral resections of the prostate (TURPS). The mechanisms regulating the growth of CRPC bone and visceral metastases have not been explored in depth due to the paucity of patient-related material available for analysis. In this study, we aim to evaluate SRF protein expression in prostate cancer (PCa) metastases, which has not previously been reported.
      547Scopus© Citations 15
  • Publication
    Innovative Technologies Changing Cancer Treatment
    Conventional therapies for cancer such as chemotherapy and radiotherapy remain a mainstay in treatment, but in many cases a targeted approach is lacking, and patients can be vulnerable to drug resistance. In recent years, novel concepts have been emerging to improve the traditional therapeutic options in cancers with poor survival outcomes. New therapeutic strategies involving areas like energy metabolism and extracellular vesicles along with advances in immunotherapy and nanotechnology are driving the next generation of cancer treatments. The development of fields such as theranostics in nanomedicine is also opening new doors for targeted drug delivery and nano-imaging. Here we discuss the use of innovative technologies presented at the Irish Association for Cancer Research (IACR) Annual Meeting, highlighting examples of where new approaches may lead to promising new treatment options for a range of cancer types.
      326Scopus© Citations 19
  • Publication
    Role of serum response factor expression in prostate cancer biochemical recurrence
    Background: Up to a third of prostate cancer patients fail curative treatment strategiessuch as surgery and radiation therapy in the form of biochemical recurrence (BCR) whichcan be predictive of poor outcome. Recent clinical trials have shown that menexperiencing BCR might benefit from earlier intervention post-radical prostatectomy(RP). Therefore, there is an urgent need to identify earlier prognostic biomarkers whichwill guide clinicians in making accurate diagnosis and timely decisions on the nextappropriate treatment. The objective of this study was to evaluate Serum ResponseFactor (SRF) protein expression following RP and to investigate its association with BCR.Materials and Methods: SRF nuclear expression was evaluated by immunohistochemistry(IHC) in TMAs across three international radical prostatectomy cohorts for a totalof 615 patients. Log-rank test and Kaplan-Meier analyses were used for BCRcomparisons. Stepwise backwards elimination proportional hazard regression analysiswas used to explore the significance of SRF in predicting BCR in the context of otherclinical pathological variables. Area under the curve (AUC) values were generated bysimulating repeated random sub-samples.Results: Analysis of the immunohistochemical staining of benign versus cancer coresshowed higher expression of nuclear SRF protein expression in cancer cores comparedwith benign for all the three TMAs analysed (P < 0.001, n = 615). Kaplan-Meier curves ofthe three TMAs combined showed that patients with higher SRF nuclear expression hada shorter time to BCR compared with patients with lower SRF expression (P < 0.001,n = 215). Together with pathological T stage T3, SRF was identified as a predictor of BCRusing stepwise backwards elimination proportional hazard regression analysis(P = 0.0521). Moreover ROC curves and AUC values showed that SRF was betterthan T stage in predicting BCR at year 3 and 5 following radical prostatectomy, thecombination of SRF and T stage had a higher AUC value than the two taken separately.Conclusions: SRF assessment by IHC following RP could be useful in guiding cliniciansto better identify patients for appropriate follow-up and timely treatment.
      435Scopus© Citations 8
  • Publication
    Relationship between serum response factor and androgen receptor in prostate cancer
    Background: Serum response factor (SRF) is an important transcription factor in castrate-resistant prostate cancer (CRPC). Since CRPC is associated with androgen receptor (AR) hypersensitivity, we investigated the relationship between SRF and AR. Materials and Methods: Transcriptional activity was assessed by luciferase assay. Cell proliferation was measured by MTT and flow cytometry. Protein expression in patients was assessed by immunohistochemistry. Results: To investigate AR involvement in SRF response to androgen, AR expression was down-regulated using siRNA. This resulted in the abrogation of SRF induction post-DHT. Moreover, DHT stimulation failed to induce SRF transcriptional activity in AR-negative PC346 DCC cells, which was only restored following AR over-expression. Next, SRF expression was down-regulated by siRNA, resulting in AR increased transcriptional activity in castrate-resistant LNCaP Abl cells but not in the parental LNCaP. This negative feedback loop in the resistant cells was confirmed by immunohistochemistry which showed a negative correlation between AR and SRF expression in CRPC bone metastases and a positive correlation in androgen-naïve prostatectomies. Cell proliferation was next assessed following SRF inhibition, demonstrating that SRF inhibition is more effective than AR inhibition in castrate-resistant cells. Conclusion: Our data support SRF as a promising therapeutic target in combination with current treatments. Prostate 75:1704–1717, 2015. © 2015 Wiley Periodicals, Inc.
      507Scopus© Citations 6