Genetic profiling of hormone-sensitive and castration-resistant prostate cancers and identification of genetic mutations prone to castration-resistant prostate cancer

Wang, Ze; Yan, Xuzhi; Tang, Peng; Tang, Tang; Wang, Yapeng; Song, Peng; Wang, Shuo; Lan, Weihua; Wang, Luofu; Zhang, Yao; Zhang, Jun; Li, Ke; Shu, Zehua; Xu, Jing; Qin, Jun; Zhang, Dianzheng; Jiang, Jun; Liu, Qiuli

doi:10.1038/s41391-022-00618-2

Cited by 9 publications

(4 citation statements)

References 45 publications

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“…Another potential driver is the increase in androgen biosynthesis, which can occur through the mutation in the HSD3B1 gene [ 30 ]. Mutations in other genes may also contribute to the risk, and a panel of four genetic mutations ( MSH2 , CDK12 , TP53 , and RB1 ) has been proposed as a predictor of risk for early progression [ 31 ]. Complex chromosome rearrangements, or chromoplexy, which include many cancer-associated genes, have been associated with prostate cancerogenesis [ 32 ].…”

Section: Diagnosis and Therapy Of Pcmentioning

confidence: 99%

Let’s Go 3D! New Generation of Models for Evaluating Drug Response and Resistance in Prostate Cancer

Petrić

Sabol

2023

IJMS

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Prostate cancer (PC) is the third most frequently diagnosed cancer worldwide and the second most frequent in men. Several risk factors can contribute to the development of PC, and those include age, family history, and specific genetic mutations. So far, drug testing in PC, as well as in cancer research in general, has been performed on 2D cell cultures. This is mainly because of the vast benefits these models provide, including simplicity and cost effectiveness. However, it is now known that these models are exposed to much higher stiffness; lose physiological extracellular matrix on artificial plastic surfaces; and show changes in differentiation, polarization, and cell–cell communication. This leads to the loss of crucial cellular signaling pathways and changes in cell responses to stimuli when compared to in vivo conditions. Here, we emphasize the importance of a diverse collection of 3D PC models and their benefits over 2D models in drug discovery and screening from the studies done so far, outlining their benefits and limitations. We highlight the differences between the diverse types of 3D models, with the focus on tumor–stroma interactions, cell populations, and extracellular matrix composition, and we summarize various standard and novel therapies tested on 3D models of PC for the purpose of raising awareness of the possibilities for a personalized approach in PC therapy.

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Section: Diagnosis and Therapy Of Pcmentioning

confidence: 99%

Let’s Go 3D! New Generation of Models for Evaluating Drug Response and Resistance in Prostate Cancer

Petrić

Sabol

2023

IJMS

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“…Patients with mCRPC and HRR gene defects have a significantly shorter life expectancy (median overall survival: 28.5 months) than patients with mCRPC and no HRR gene defects (36 months) [ 10 ]. Furthermore, patients with metastatic castration (hormone)-sensitive prostate cancer (mCSPC) and HRR gene alterations progress to mCRPC significantly faster than those without such mutations [ 11 , 12 ]. Therefore, targeting the PARP pathway, in addition to androgen deprivation therapy in patients with mCRPC, presents a potential therapeutic strategy for improved survival.…”

Section: Introductionmentioning

confidence: 99%

Demonstrating Bioequivalence for Two Dose Strengths of Niraparib and Abiraterone Acetate Dual-Action Tablets Versus Single Agents: Utility of Clinical Study Data Supplemented with Modeling and Simulation

Yu,

Hazra,

Jiao

et al. 2024

Clin Pharmacokinet

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Background and Objective The combination of niraparib and abiraterone acetate (AA) plus prednisone is under investigation for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) and metastatic castration-sensitive prostate cancer (mCSPC). Regular-strength (RS) and lower-strength (LS) dual-action tablets (DATs), comprising niraparib 100 mg/AA 500 mg and niraparib 50 mg/AA 500 mg, respectively, were developed to reduce pill burden and improve patient experience. A bioequivalence (BE)/bioavailability (BA) study was conducted under modified fasting conditions in patients with mCRPC to support approval of the DATs. Methods This open-label randomized BA/BE study (NCT04577833) was conducted at 14 sites in the USA and Europe. The study had a sequential design, including a 21-day screening phase, a pharmacokinetic (PK) assessment phase comprising three periods [namely (1) single-dose with up to 1-week run-in, (2) daily dose on days 1–11, and (3) daily dose on days 12–22], an extension where both niraparib and AA as single-agent combination (SAC; reference) or AA alone was continued from day 23 until discontinuation, and a 30-day follow-up phase. Patients were randomly assigned in a parallel-group design (four-sequence randomization) to receive a single oral dose of niraparib 100 mg/AA 1000 mg as a LS-DAT or SAC in period 1, and patients continued as randomized into a two-way crossover design during periods 2 and 3 where they received niraparib 200 mg/AA 1000 mg once daily as a RS-DAT or SAC. The design was powered on the basis of crossover assessment of RS-DAT versus SAC. During repeated dosing (periods 2 and 3, and extension phase), all patients also received prednisone/prednisolone 5 mg twice daily. Plasma samples were collected for measurement of niraparib and abiraterone plasma concentrations. Statistical assessment of the RS-DAT and LS-DAT versus SAC was performed on log-transformed pharmacokinetic parameters data from periods 2 and 3 (crossover) and from period 1 (parallel), respectively. Additional paired analyses and model-based bioequivalence assessments were conducted to evaluate the similarity between the LS-DAT and SAC. Results For the RS-DAT versus SAC, the 90% confidence intervals (CI) of geometric mean ratios (GMR) for maximum concentration at a steady state (C max,ss ) and area under the plasma concentration–time curve from 0–24 h at a steady state (AUC 0–24h,ss ) were respectively 99.18-106.12% and 97.91-104.31% for niraparib and 87.59-106.69 and 86.91-100.23% for abiraterone. For the LS-DAT vs SAC, the 90% CI of GMR for AUC 0–72h of niraparib was 80.31-101.12% in primary analysis, the 90% CI of GMR for C max,ss and AUC 0–24h ,ss of abiraterone was 85.41-118.34% and 86.51-121.64% respectively, and 96.4% of simulated LS-DAT versus SAC BE trials met the BE criteria...

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“…Several studies have investigated the etiology and pathophysiology of PCa, but the exact mechanisms are still unknown [6]. Important roles are played by the genetic characteristics of the patients as well as its immune system [7][8][9]. The heterogeneous biological nature of the disease brings great challenges during treatment, highlighting the need for better definition of the pathophysiology of PCa [10].…”

Section: Introductionmentioning

confidence: 99%

Cancer Stem Cells and Prostate Cancer: A Narrative Review

Salhi

Sequi

Valenzi

et al. 2023

IJMS

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Cancer stem cells (CSCs) are a small and elusive subpopulation of self-renewing cancer cells with the remarkable ability to initiate, propagate, and spread malignant disease. In the past years, several authors have focused on the possible role of CSCs in PCa development and progression. PCa CSCs typically originate from a luminal prostate cell. Three main pathways are involved in the CSC development, including the Wnt, Sonic Hedgehog, and Notch signaling pathways. Studies have observed an important role for epithelial mesenchymal transition in this process as well as for some specific miRNA. These studies led to the development of studies targeting these specific pathways to improve the management of PCa development and progression. CSCs in prostate cancer represent an actual and promising field of research.

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Genetic profiling of hormone-sensitive and castration-resistant prostate cancers and identification of genetic mutations prone to castration-resistant prostate cancer

Cited by 9 publications

References 45 publications

Let’s Go 3D! New Generation of Models for Evaluating Drug Response and Resistance in Prostate Cancer

Let’s Go 3D! New Generation of Models for Evaluating Drug Response and Resistance in Prostate Cancer

Demonstrating Bioequivalence for Two Dose Strengths of Niraparib and Abiraterone Acetate Dual-Action Tablets Versus Single Agents: Utility of Clinical Study Data Supplemented with Modeling and Simulation

Cancer Stem Cells and Prostate Cancer: A Narrative Review

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