Niven Mehra
A5036825889- Prostate Cancer Treatment and Research
- Radiopharmaceutical Chemistry and Applications
- Cancer, Lipids, and Metabolism
- Cancer Genomics and Diagnostics
- PARP inhibition in cancer therapy
- Prostate Cancer Diagnosis and Treatment
- Cancer Immunotherapy and Biomarkers
- Bladder and Urothelial Cancer Treatments
- Urinary and Genital Oncology Studies
- Immunotherapy and Immune Responses
- Inflammatory Biomarkers in Disease Prognosis
- Cancer Cells and Metastasis
- BRCA gene mutations in cancer
- DNA Repair Mechanisms
- Bone health and treatments
- Immune cells in cancer
- Mass Spectrometry Techniques and Applications
- Multiple Myeloma Research and Treatments
- Cancer, Hypoxia, and Metabolism
- Peptidase Inhibition and Analysis
- Cancer Treatment and Pharmacology
- Radiation Therapy and Dosimetry
- Statistical Methods in Clinical Trials
- Epigenetics and DNA Methylation
- Mathematical Biology Tumor Growth
Radboud University Nijmegen
2017-2025
Radboud University Medical Center
2017-2025
Radboud Institute for Molecular Life Sciences
2018-2024
University Medical Center
2019-2023
Stichting Kinderoncologie Nederland
2023
Ospedale Santa Chiara
2022
Hospital Universitario 12 De Octubre
2022
Institute of Cancer Research
2015-2021
Royal Marsden Hospital
2014-2021
University of London
2021
Multiple loss-of-function alterations in genes that are involved DNA repair, including homologous recombination associated with response to poly(adenosine diphosphate–ribose) polymerase (PARP) inhibition patients prostate and other cancers.
BACKGROUND: Preclinical studies and results of a phase 2 trial abiraterone olaparib suggest combined antitumor effect when the poly(adenosine diphosphate[ADP]-ribose) polymerase inhibitor is with next-generation hormonal agent to treat metastatic castration-resistant prostate cancer (mCRPC). METHODS: We conducted double-blind, 3 versus placebo in patients mCRPC first-line setting. Patients were enrolled regardless homologous recombination repair gene mutation (HRRm) status. HRRm status was...
Metastatic castration-resistant prostate cancer (mCRPC) has a highly complex genomic landscape. With the recent development of novel treatments, accurate stratification strategies are needed. Here we present whole-genome sequencing (WGS) analysis fresh-frozen metastatic biopsies from 197 mCRPC patients. Using unsupervised clustering based on features, define eight distinct clusters. We observe potentially clinically relevant genotypes, including microsatellite instability (MSI), homologous...
Innovations in imaging and molecular characterisation the evolution of new therapies have improved outcomes advanced prostate cancer. Nonetheless, we continue to lack high-level evidence on a variety clinical topics that greatly impact daily practice. To supplement evidence-based guidelines, 2022 Advanced Prostate Cancer Consensus Conference (APCCC 2022) surveyed experts about key dilemmas management.To present consensus voting results for select questions from APCCC 2022.Before conference,...
11 Background: Preclinical studies have shown combined anti-tumor effect through interactions between poly(adenosine diphosphate–ribose) polymerase and androgen receptor signaling pathways. A Phase II trial (NCT01972217) in pts with mCRPC unselected by homologous recombination repair (HRR) status who previously received docetaxel demonstrated improved radiographic progression-free survival (rPFS) for treated ola + abi vs pbo (Clarke N, 2018). The III PROpel study (NCT03732820) evaluates the...
Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets involved in cancer progression and considered a promising biosource detection, as they alter their RNA content upon local systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood tests enable the of 18 types. With 99% specificity asymptomatic controls, thromboSeq correctly detected presence two-thirds 1,096 samples stage I–IV half 352 I–III...
There is an unmet need for therapeutic options that prolong survival patients with heavily pretreated, metastatic castration-resistant prostate cancer (mCRPC). The phase III, open-label KEYLYNK-010 study evaluated pembrolizumab plus olaparib versus a next-generation hormonal agent (NHA) biomarker-unselected, previously treated mCRPC.
No consensus strategies exist for prognosticating metastatic castration-resistant prostate cancer (mCRPC). Circulating tumor DNA fraction (ctDNA%) is increasingly reported by commercial and laboratory tests but its utility risk stratification unclear. Here, we intersect ctDNA%, treatment outcomes, clinical characteristics across 738 plasma samples from 491 male mCRPC patients two randomized multicentre phase II trials a prospective province-wide blood biobanking program. ctDNA% correlates...
Innovations have improved outcomes in advanced prostate cancer (PC). Nonetheless, we continue to lack high-level evidence on a variety of topics that greatly impact daily practice. The 2024 Advanced Prostate Cancer Consensus Conference (APCCC) surveyed experts key questions clinical management order supplement evidence-based guidelines. Here present voting results for from APCCC 2024.
Abstract Purpose: Circulating tumor cells (CTCs) have clinical relevance, but their study has been limited by low frequency. Experimental Design: We evaluated liquid biopsies apheresis to increase CTC yield from patients suffering metastatic prostate cancer, allow precise gene copy-number calls, and disease heterogeneity. Results: Apheresis was well tolerated allowed the separation of large numbers CTCs; average 7.5 mL peripheral blood 167 CTCs, whereas per (mean volume: 59.5 mL) 12,546...
Noninvasive biomarkers are needed to guide metastatic castration-resistant prostate cancer (mCRPC) treatment. To clinically qualify baseline and on-treatment cell-free DNA (cfDNA) concentrations as of patient outcome following taxane chemotherapy. Blood for cfDNA analyses was prospectively collected from 571 mCRPC patients participating in two phase III clinical trials, FIRSTANA (NCT01308567) PROSELICA (NCT01308580). Patients received docetaxel (75 mg/m2) or cabazitaxel (20 25 first-line...
<h3>Importance</h3> DNA repair gene aberrations occur in 20% to 30% of patients with castration-resistant prostate cancer (CRPC), and some these have been associated sensitivity poly(ADP-ribose) polymerase (PARP) inhibition or platinum-based treatments. However, previous trials assessing treatments CRPC mostly included a biomarker-unselected population; therefore, efficacy is unknown. <h3>Objective</h3> To characterize the antitumor activity therapies men without alterations. <h3>Design,...
<h3>Background</h3> Clinical benefit of cellular immunotherapy has been shown in patients with castration-resistant prostate cancer (CRPC)<b>.</b> We investigated the immunological response and clinical outcome vaccination blood-derived CD1c<sup>+</sup> myeloid dendritic cells (mDCs; cDC2) plasmacytoid DCs (pDCs). <h3>Methods</h3> In this randomized phase IIa trial<b>,</b> 21 chemo-naive CRPC received maximally 9 vaccinations mature mDCs, pDCs or a combination mDCs plus pDCs. were stimulated...
Abstract Purpose: [177Lu]Lu-PSMA-617 radioligand therapy (177Lu-PSMA) is a novel treatment for metastatic castration-resistant prostate cancer (mCRPC), which could also be applied to patients with hormone-sensitive (mHSPC) PSMA expression. In this prospective study (NCT03828838), we analyzed toxicity, radiation doses, and effect of 177Lu-PSMA in pateints low-volume mHSPC. Patients Methods: Ten progressive mHSPC following local treatment, maximum ten lesions on [68Ga]Ga-PSMA-11...
Activation of the PI3K/AKT/mTOR pathway through loss phosphatase and tensin homolog (PTEN) occurs in approximately 50% patients with metastatic castration-resistant prostate cancer (mCRPC). Recent evidence suggests that combined inhibition androgen receptor (AR) AKT may be beneficial mCRPC PTEN loss.
Abstract Purpose: Successful implementation of genomic testing in clinical practice is critical for identification men with metastatic castration-resistant prostate cancer (mCRPC) eligible olaparib and future molecularly targeted therapies. Patients Methods: An investigational trial assay, based on the FoundationOneCDx tissue test, was used to prospectively identify patients qualifying homologous recombination repair gene alterations phase III PROfound study. Evaluation next-generation...
While [177Lu]Lu-PSMA radioligand therapy is currently only applied in end-stage metastatic castrate-resistant prostate cancer (mCRPC) patients, also low-volume hormone-sensitive (mHSPC) patients can benefit from it. However, there are toxicity concerns related to the sink effect disease. This prospective study aims determine kinetics of mHSPC analyzing doses organs at risk (salivary glands, kidneys, liver, and bone marrow) tumor lesions < 1 cm diameter.Ten underwent two cycles therapy....