Genetic Testing in Prostate Cancer

AbstractPurpose of ReviewThis review summarizes recent advances in prostate cancer (PCa) genetics.Recent FindingsUpwards of 20% of metastatic castration-resistant prostate tumors (mCRPC) carry homologous recombination (HR) repair gene mutations, of which ~  10% are germline (inherited). Another ~ 5% exhibit microsatellite instability (MSI-H) and/or mismatch repair deficiency (MMRd). Pembrolizumab is approved for tumors with MMRd, thus patients with mCRPC and MMRd are candidates for pembrolizumab. Emerging data indicate that platinum chemotherapy a nd poly ADP-ribose polymerase inhibitors (PARPi) are effective in PCa exhibiting HR deficiency. NCCN guidelines now recommend germline and somatic tumor testing in specific clinical scenarios due to treatment and family implications.SummaryGenetic testing in PCa patients may inform prognosis, treatment options, and have implications for family counseling. PARPi, platinum chemotherapy, and immune checkpoint inhibitors are promising targeted therapies for PCa with specific molecular features. Therapeutic advances, along with importance to relatives, are driving genetic testing in prostate cancer.
Source: Current Oncology Reports - Category: Cancer & Oncology Source Type: research

Related Links:

RARITAN, N.J., February 3, 2020 – The Janssen Pharmaceutical Companies of Johnson &Johnson announced today multiple data presentations from a robust solid tumor portfolio that will be featured at the American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, taking place February 13-15 in San Francisco. Company-sponsored data presentations will include clinical results for ERLEADA® (apalutamide) and niraparib in prostate cancer; and BALVERSA™ (erdafitinib) in bladder cancer. “We are committed to improving outcomes in patients with prostate and bladder cancer where high unmet ...
Source: Johnson and Johnson - Category: Pharmaceuticals Tags: Innovation Source Type: news
In this study, we engineered the polycation nanoparticle (NP), which co-encapsulated DNA damage repair inhibitor Dbait and chemotherapeutic drug Docetaxel (Dtxl), using H1 nanopolymer (folate--polyethylenimine600-cyclodextrin), and the size of H1/Dbait/Dtxl was about 117 nm. We demonstrated that H1/Dbait/Dtxl enhanced the efficiency of radio-chemotherapy in prostate cancer cells by CCK-8 assay and colony-forming assay. Importantly, the improvement of radio-chemotherapy of H1/Dbait/Dtxl in prostate cancer was also validated in vivo, and the NP did not have a high toxicity profile. The results of immunohistochemi...
Source: Artificial Cells, Nanomedicine and Biotechnology - Category: Biotechnology Tags: Artif Cells Nanomed Biotechnol Source Type: research
AbstractBackgroundPoly(ADP-ribose) polymerases (PARPs) play a key role in DNA damage repair (DDR). DDR defects due to HRRm (eg BRCA mutation [BRCAm]) or resulting in HRD (eg global loss of heterozygosity) may sensitize tumors to PARP inhibitors, eg olaparib. Olaparib monotherapy has activity in BRCAm ovarian, breast, pancreatic, and prostate cancer, and in prostate cancer with DDR defects beyond BRCAm (TOPARP). Olaparib improved efficacy outcomes vs placebo/chemotherapy as treatment in  ≤ 3rd-line (3L) HER2-negative BRCAm breast cancer (OlympiAD) and ≥2L BRCAm ovarian cancer (SOLO3), and maintenance the...
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
This study aims to clarify the potential role and molecular mechanisms of GRIM-19 on the response of PC cells to chemical drug docetaxel. mRNA and protein level of GRIM-19 expression in cells and tissues of PC were measured by quantitative real-time PCR and western blot, respectively. Knock-down of GRIM-19 in PC cells was performed using siRNA. Cell apoptosis was determined by flow cytometric analysis. DNA damage in PC cells was detected by γ-H2AX staining. GRIM-19 was downregulated in PC tissues and cell lines. Knockdown of GRIM-19 increased the resistance of PC cells to docetaxel, and overexpression of GRIM-19 prom...
Source: Clinical and Experimental Pharmacology and Physiology - Category: Drugs & Pharmacology Authors: Tags: Clin Exp Pharmacol Physiol Source Type: research
CONCLUSIONS: Leveraging large-scale transcriptomic data allowed the identification of an aggressive subtype of treatment-naïve primary prostate cancer that harbors molecular features more analogous to mCRPC. This suggests that a pre-existing subgroup of patients may have tumors that are predisposed to fail multiple current standard of care therapies and warrant dedicated therapeutic investigation. PMID: 31515456 [PubMed - as supplied by publisher]
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
In conclusion, our data show how oncogenic and tumor-suppressive drivers of cellular senescence act to regulate surveillance processes that can be circumvented to enable SnCs to elude immune recognition but can be reversed by cell surface-targeted interventions to purge the SnCs that persist in vitro and in patients. Since eliminating SnCs can prevent tumor progression, delay the onset of degenerative diseases, and restore fitness; since NKG2D-Ls are not widely expressed in healthy human tissues and NKG2D-L shedding is an evasion mechanism also employed by tumor cells; and since increasing numbers of B cells express NKG2D ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In conclusion, our data show how oncogenic and tumor-suppressive drivers of cellular senescence regulate surveillance processes that can be circumvented to enable SnCs to elude immune recognition but can be reversed by cell surface-targeted interventions to purge the SnCs that persist in vitro and in patients. Since eliminating SnCs can prevent tumor progression, delay the onset of degenerative diseases, and restore fitness; since NKG2D-Ls are not widely expressed in healthy human tissues and NKG2D-L shedding is an evasion mechanism also employed by tumor cells; and since increasing numbers of B cells express NKG2D ligands...
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs
In this study, we identify a link between members of the genus Veillonella and exercise performance. We observed an increase in Veillonella relative abundance in marathon runners postmarathon and isolated a strain of Veillonella atypica from stool samples. Inoculation of this strain into mice significantly increased exhaustive treadmill run time. Veillonella utilize lactate as their sole carbon source, which prompted us to perform a shotgun metagenomic analysis in a cohort of elite athletes, finding that every gene in a major pathway metabolizing lactate to propionate is at higher relative abundance postexercise. Us...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Purpose of review An overview of urologic malignancies in Lynch syndrome and the current state of research. Recent findings Upper tract urothelial carcinoma (UTUC) is the third most common malignancy in Lynch syndrome. Establishment and utilization of a sensitive and practical screening method for Lynch syndrome in patients presenting with UTUC is overdue. Next-generation sequencing to evaluate for microsatellite instability (MSI) and detect mutations of mismatch repair (MMR) genes may be the future of Lynch syndrome screening. Epidemiologic data and molecular characterization suggest bladder urothelial carcinoma (BUC...
Source: Current Opinion in Urology - Category: Urology & Nephrology Tags: CANCER GENETICS IN UROLOGIC PRACTICE: Edited by Todd M. Morgan and Brian Chapin Source Type: research
Purpose of review The utility of tumor genetic testing in metastatic prostate cancer is rapidly evolving – especially in respect to finding prognostic and predictive biomarkers. In this review, we describe genomic aberrations in clinically relevant pathways in metastatic castration-resistant prostate cancer (mCRPC) for which therapeutic targeting is possible. Recent findings Recognizing the diverse array of genetic features within prostate cancer, the goal of testing in mCRPC is to match an individual patients’ tumor with the best therapy. Approximately 20–25% of mCRPC patients have defects in DNA re...
Source: Current Opinion in Urology - Category: Urology & Nephrology Tags: CANCER GENETICS IN UROLOGIC PRACTICE: Edited by Todd M. Morgan and Brian Chapin Source Type: research
More News: Cancer | Cancer & Oncology | Chemotherapy | Gastroschisis Repair | Genetics | Prostate Cancer