BRCA Mutations in Prostate Cancer: Prognostic and Predictive Implications.

BRCA Mutations in Prostate Cancer: Prognostic and Predictive Implications. J Oncol. 2020;2020:4986365 Authors: Messina C, Cattrini C, Soldato D, Vallome G, Caffo O, Castro E, Olmos D, Boccardo F, Zanardi E Abstract Despite chemotherapy and novel androgen-receptor signalling inhibitors (ARSi) have been approved during the last decades, metastatic castration-resistant prostate cancer (mCRPC) remains a lethal disease with poor clinical outcomes. Several studies found that germline or acquired DNA damage repair (DDR) defects affect a high percentage of mCRPC patients. Among DDR defects, BRCA mutations show relevant clinical implications. BRCA mutations are associated with adverse clinical features in primary tumors and with poor outcomes in patients with mCRPC. In addition, BRCA mutations predict good response to poly-ADP ribose polymerase (PARP) inhibitors, such as olaparib, rucaparib, and niraparib. However, concerns still remain on the role of extensive mutational testing in prostate cancer patients, given the implications for patients and for their progeny. The present comprehensive review attempts to provide an overview of BRCA mutations in prostate cancer, focusing on their prognostic and predictive roles. PMID: 32963528 [PubMed]
Source: Journal of Oncology - Category: Cancer & Oncology Tags: J Oncol Source Type: research

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Mismatch repair-deficient (dMMR) prostate cancer is rare and has not been well studied. We aimed to evaluate the clinical characterization of dMMR metastatic castration-resistant prostate cancer (mCRPC) patients. The MMR genes include MLH1, MLH3, MSH2, MSH6, PMS1, PMS2, and EPCAM, and were analyzed by targeted sequencing of plasma cell-free DNA samples. A total of 109 mCRPC patients were identified, including 50 patients with MMR alterations (pathogenic alterations, n = 7; alterations of unknown significance, n = 43) and 59 patients with wild-type MMR. For the seven patients with pathogenic MMR alterations, the median age ...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
CONCLUSIONS: These data show the implementation of immunotherapy as a novel alternative against renal and bladder cancer. The arrival of new agents for advanced urothelial carcinoma should be highlighted, and the efficacy of enzalutamide and apalutamide in de novo metastatic prostate cancer is established. In metastatic CRPC, cabazitaxel and olaparib (targeting mutations) are promising therapeutic options. PMID: 32948345 [PubMed - as supplied by publisher]
Source: Actas Urologicas Espanolas - Category: Urology & Nephrology Authors: Tags: Actas Urol Esp Source Type: research
Publication date: Available online 2 July 2020Source: European UrologyAuthor(s): Francesco Massari, Veronica Mollica
Source: European Urology - Category: Urology & Nephrology Source Type: research
Abstract Sumoylation is the Posttranslational modification gaining most of the research interest recently. Sumoylation is involved in various crucial functions of the cell such as regulation of cell cycle, DNA damage repair, apoptosis etc. Oncology is advancing in radiotherapy, targeted chemotherapy, various forms of immunotherapy and targeted gene therapy. Researches are being conducted to prove its connotation with a variety of cancers and inhibitors are being developed to obstruct the fatal effect caused by misbalance of the SUMO-catalytic cycle. It has been shown that upregulation of certain enzymes of Sumoyla...
Source: Current Pharmaceutical Design - Category: Drugs & Pharmacology Authors: Tags: Curr Pharm Des Source Type: research
Defective BRCA genes are well known for their ability to cause breast and ovarian cancers in women. But these same gene defects are also strong risk factors for aggressive prostate cancer in men. About 10% of men with metastatic prostate cancer — meaning cancer that is spreading away from the prostate — test positive for genetic mutations in BRCA genes. Fortunately, these cancers can be treated with new types of personalized therapies. In May, the FDA approved two new drugs specifically for men with BRCA-positive metastatic prostate cancer that has stopped responding to other treatments. One of the drugs, calle...
Source: Harvard Health Blog - Category: Consumer Health News Authors: Tags: Health Prostate Knowledge Treatments HPK Source Type: blogs
The combined clinical and molecular heterogeneity of prostate cancer necessitates the use of prognostic, predictive, and diagnostic biomarkers to assist the clinician with treatment selection. The pathologist plays a critical role in guiding molecular biomarker testing in prostate cancer and requires a thorough knowledge of the current testing options. In the setting of clinically localized prostate cancer, prognostic biomarkers such as Ki-67 labeling, PTEN loss or mRNA-based genomic signatures can be useful to help determine whether definitive therapy is required. In the setting of advanced disease, predictive biomarkers,...
Source: The American Journal of Surgical Pathology - Category: Pathology Tags: Special Articles Source Type: research
ew D. Beggs Radiotherapy is routinely used as a neoadjuvant, adjuvant or palliative treatment in various cancers. There is significant variation in clinical response to radiotherapy with or without traditional chemotherapy. Patients with a good response to radiotherapy demonstrate better clinical outcomes universally across different cancers. The PI3K/AKT/mTOR pathway upregulation has been linked to radiotherapy resistance. We reviewed the current literature exploring the role of inhibiting targets along this pathway, in enhancing radiotherapy response. We identified several studies using in vitro cancer cell lines, in...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
(Institute of Cancer Research) A drug already licensed for the treatment of breast and ovarian cancers is more effective than targeted hormone therapy at keeping cancer in check in some men with advanced prostate cancer, a major clinical trial reports.Olaparib, a pill lacking the side effects of chemotherapy, can target an Achilles heel in prostate cancers with a weakness in their ability to repair damaged DNA.
Source: EurekAlert! - Cancer - Category: Cancer & Oncology Source Type: news
Immunotherapy has revolutionized the treatment of both hematological malignancies and solid tumors. The use of immunotherapy has improved outcome for patients with cancer across multiple tumor types, including lung, melanoma, ovarian, genitourinary, and more recently breast cancer with durable responses seen even in patients with widespread metastatic disease. Despite the promising results, immunotherapy still helps only a subset of patients due to overall low response rates. Moreover, the response to immunotherapy is highly cancer specific and results have not been as promising in cancers that are considered less immunoge...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Grünwald V Abstract For decades, the treatment of advanced prostate cancer was mainly based on the manipulation of the androgen receptor-controlled proliferation pathway. Chemotherapy only played an additional important role with the advent of taxanes. The progress in translational research in recent years has led to innovations in the therapeutic environment. With the decoding of the homologous repair deficiency (HRD) machinery and its ability to be influenced by PARP inhibitors, targeted therapies moved into the therapeutic focus for selected patients. The first positive phase III study for PARP inhib...
Source: Der Urologe. Ausg. A - Category: Urology & Nephrology Authors: Tags: Urologe A Source Type: research
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