Multifaceted and personalized therapy of advanced prostate cancer

Purpose of review: A number of molecular and genomic biomarkers that possess the ability to guide treatment or ‘actionable targets’ are being reported in metastatic prostate cancer. In addition, pathways of resistance to existing therapies and novel agents to overcome them are currently under active investigation. The next wave of investigations is focused on personalized therapy of prostate cancer. The focus of this review article is to provide an update on clinical development in advanced prostate cancer and to highlight the ongoing investigations of biomarker discovery, and ways of overcoming therapeutic resistance. The next generation of clinical trials developing novel targets and compounds promises to be in populations enriched with specific marker expression. Recent findings: The breakthrough report, of the ability of the androgen receptor variant 7 mutation, detected in circulating tumor cells, to predict the lack of response to abiraterone or enzalutamide, and the remarkable responses of poly adenosine diphosphate ribose polymerase inhibitors in prostate cancer with DNA repair mutations have elevated hopes of a bright future in the biomarker-driven therapeutic arena. Novel targets such as bromodomain extra terminal-1 and phosphatidylinositol 3-kinase hold promise for the possibility of overcoming resistance. Novel hormone agents are also under active study. Summary: As the clinical application of the multifaceted therapies narrows down to enriched patie...
Source: Current Opinion in Oncology - Category: Cancer & Oncology Tags: GENITOURINARY SYSTEM: Edited by Arif Hussain Source Type: research

Related Links:

AbstractPurpose of ReviewTo describe the epidemiology, pathogenesis, and management of vesicourethral anastomotic stenosis after prostate cancer treatment.Recent FindingsInjectable scar modulating agents administered at the time of direct visual internal urethrotomy of vesicourethral anastomotic stenoses have been shown to improve endoscopic treatment outcomes. Trials are ongoing to find the optimal agent and delivery system. Novel tissue engineering techniques are in development and hold promise.SummaryVesicourethral anastomotic stenosis after the treatment of prostate cancer is a challenging complication for patients and...
Source: Current Bladder Dysfunction Reports - Category: Urology & Nephrology Source Type: research
Authors: Schepisi G, Brighi N, Cursano MC, Gurioli G, Ravaglia G, Altavilla A, Burgio SL, Testoni S, Menna C, Farolfi A, Casadei C, Tonini G, Santini D, De Giorgi U Abstract Immunotherapy represents the new era of cancer treatment because of its promising results in various cancer types. In urological tumors, the use of the immune-checkpoint inhibitors (ICIs) is increasingly spreading. Although not all patients and not all diseases respond equally well to immunotherapy, there is an increasing need to find predictive markers of response to ICIs. Patient- and tumor-related factors may be involved in primary and secon...
Source: Journal of Oncology - Category: Cancer & Oncology Tags: J Oncol Source Type: research
Authors: Morgans AK, Szymaniak BM Abstract The landscape of genetic testing for prostate cancer is rapidly evolving. There is increasing evidence that individuals with germline mutations in DNA-repair genes are more responsive to targeted therapies. Due to potential implications for treatment, these genes should be taken into consideration when determining the scope of genetic testing. PMID: 31629435 [PubMed - in process]
Source: Canadian Journal of Urology - Category: Urology & Nephrology Tags: Can J Urol Source Type: research
Authors: Carroll PR, Witte JS, Parsons JK Abstract Men with germline mutations in DNA repair genes are at an increased risk of prostate cancer. These germline mutations are commonly seen in conjunction with somatic DNA repair gene mutations in prostate tumors. This indicates that men with a personal or family history of prostate cancer-as well as other cancer syndromes arising from mutations in DNA repair genes-should be considered for genetic testing and counseling. PMID: 31629425 [PubMed - in process]
Source: Canadian Journal of Urology - Category: Urology & Nephrology Tags: Can J Urol Source Type: research
This article summarizes a presentation at the 2019 Philadelphia Consensus Conference focused on the latest data at the intersection of germline and tumor genetic testing for prostate cancer patients. PMID: 31629422 [PubMed - in process]
Source: Canadian Journal of Urology - Category: Urology & Nephrology Tags: Can J Urol Source Type: research
Authors: Knudsen KE Abstract Despite significant advances in understanding the biology of advanced prostate cancer and approval of novel therapeutic agents, there is no durable cure for metastatic disease. Recent findings unmasked the importance of androgen receptor (AR) signaling in regulation of DNA repair, and alterations of the AR-DNA repair factor axis were shown to promote aggressive phenotypes including metastasis. These and related findings underscore the importance of determining impact AR-DNA repair factor alterations on prostate cancer progression. PMID: 31629421 [PubMed - in process]
Source: Canadian Journal of Urology - Category: Urology & Nephrology Tags: Can J Urol Source Type: research
Authors: Cheng HH Abstract Recent studies demonstrate that the prevalence of germline mutations in DNA repair genes in metastatic prostate cancer is higher than previously recognized, and is higher than in localized disease and in unaffected men. This is compelling evidence that specific gene dysfunction is critical in prostate cancer initiation and/or evolution to metastases. Applications to treatment in advanced disease are imminent, and further investigation in early-stage disease, as well as in diverse and at-risk populations will help maximize clinical benefit. PMID: 31629420 [PubMed - in process]
Source: Canadian Journal of Urology - Category: Urology & Nephrology Tags: Can J Urol Source Type: research
Authors: Boyle J, Cooney KA Abstract Germline pathogenic mutations in DNA repair genes have been linked to prostate cancer risk and aggressiveness. This observation was facilitated by tumor sequencing of men with advanced prostate cancer and has important implications for clinical management. In addition, cascade testing will identify at-risk individuals who should be assessed for cancer risk. PMID: 31629416 [PubMed - in process]
Source: Canadian Journal of Urology - Category: Urology & Nephrology Tags: Can J Urol Source Type: research
This study aims to reveal the role of the androgen receptor (AR) in EBRT-induced DDR and to investigate whether next-generation AR inhibitor apalutamide can radiosensitize PCa. PCa cell lines and tissue slices were treated with anti-androgen alone or combined with EBRT. The effect of treatments on cell growth, tissue viability, DDR, and cell cycle were investigated. RAD51 and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) levels were determined by Western blotting. Homologous recombination (HR) capacity was measured with the directed repeats-green fluorescent protein (DR-GFP) assay. We report the radiosensitizin...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Publication date: Available online 13 October 2019Source: Seminars in Cancer BiologyAuthor(s): Vikram Shaw, Suyash Srivastava, Sanjay K. SrivastavaAbstractThe recent development of high throughput compound screening has allowed drug repurposing to emerge as an effective avenue for discovering novel treatments for cancer. FDA-approved antipsychotic drugs fluspirilene, penfluridol, and pimozide are clinically used for the treatment of psychotic disorders, primarily schizophrenia. These compounds, belong to diphenylbutylpiperidine class of antipsychotic drugs, are the potent inhibitors of dopamine D2 receptor and calcium chan...
Source: Seminars in Cancer Biology - Category: Cancer & Oncology Source Type: research
More News: Cancer | Cancer & Oncology | Clinical Trials | Gastroschisis Repair | Hormones | Prostate Cancer | Study