Publications by authors named "Gemma Fowler"
Article Synopsis
- - PARP inhibitors show promise in treating castration-resistant prostate cancer (CRPC) with homologous recombination repair (HRR) defects, but the reasons behind resistance are not completely understood.
- - A study from the TOPARP-B trial found that 79% of BRCA2/PALB2-mutated tumors exhibited reversion mutations at the end of treatment, with many related to POLQ-mediated DNA repair mechanisms.
- - In cases of BRCA2 homozygous deletions, rare subclones lacking the BRCA2 deletion are selected for after PARP inhibitor treatment, indicating the necessity for restored HRR function in developing resistance.
Prostate cancer is the most common cancer in men and it is estimated that over 350,000 men worldwide die of prostate cancer every year. There remains an unmet clinical need to improve how clinically significant prostate cancer is diagnosed and develop new treatments for advanced disease. Aberrant glycosylation is a hallmark of cancer implicated in tumour growth, metastasis, and immune evasion.
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- - Researchers found that HER3, a protein often overexpressed in aggressive prostate cancer, is linked to faster progression to castration resistance and lower survival rates.
- - The study identified that NRG1, a ligand for HER3, is primarily produced by certain immune cells in the tumor environment, and its presence promotes cancer cell growth.
- - Targeting HER3 with specific therapies, like the antibody-drug conjugate U3-1402, shows promise in fighting HER3-positive prostate cancer, suggesting the need for further clinical trials.
Article Synopsis
- Better blood tests are needed for metastatic castration-resistant prostate cancer (mCRPC) to guide treatment decisions, and low-pass whole-genome sequencing (lpWGS) of circulating tumor DNA (ctDNA) shows promise in providing insights into mCRPC behavior.
- The study examined plasma lpWGS data from 188 mCRPC patients undergoing two phase 3 clinical trials, with an aim to assess its prognostic value and its ability to correlate with treatment response.
- Findings suggest that plasma tumor fraction is a strong predictor of overall survival and is more informative than existing biomarkers, while genomic instability indicated by large-scale transition scores was linked to previous treatments but not to others like taxane or radiation therapy.*
Background: Metastatic castration-resistant prostate cancer is enriched in DNA damage response (DDR) gene aberrations. The TOPARP-B trial aims to prospectively validate the association between DDR gene aberrations and response to olaparib in metastatic castration-resistant prostate cancer.
Methods: In this open-label, investigator-initiated, randomised phase 2 trial following a selection (or pick-the-winner) design, we recruited participants from 17 UK hospitals.
Background: Detection of androgen receptor splice variant-7 (AR-V7) mRNA in circulating tumour cells (CTCs) is associated with worse outcome in metastatic castration-resistant prostate cancer (mCRPC). However, studies rarely report comparisons with CTC counts and biopsy AR-V7 protein expression.
Objective: To determine the reproducibility of AdnaTest CTC AR-V7 testing, and associations with clinical characteristics, CellSearch CTC counts, tumour biopsy AR-V7 protein expression and overall survival (OS).
The presence of high expressing epithelial cell adhesion molecule (EpCAM) circulating tumor cells (CTC) enumerated by CellSearch in blood of cancer patients is strongly associated with poor prognosis. This raises the question about the presence and relation with clinical outcome of low EpCAM expressing CTC (EpCAM CTC). In the EU-FP7 CTC-Trap program, we investigated the presence of EpCAM and EpCAM CTC using CellSearch, followed by microfiltration of the EpCAM CTC depleted blood.
View Article and Find Full Text PDFCirculating tumor cells (CTCs) have clinical relevance, but their study has been limited by their low frequency. We evaluated liquid biopsies by apheresis to increase CTC yield from patients suffering from metastatic prostate cancer, allow precise gene copy-number calls, and study disease heterogeneity. Apheresis was well tolerated and allowed the separation of large numbers of CTCs; the average CTC yield from 7.
View Article and Find Full Text PDFFrequently, the number of circulating tumor cells (CTC) isolated in 7.5 mL of blood is too small to reliably determine tumor heterogeneity and to be representative as a "liquid biopsy". In the EU FP7 program CTCTrap, we aimed to validate and optimize the recently introduced Diagnostic LeukApheresis (DLA) to screen liters of blood.
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- The study investigates the role of Circulating Tumor Cells (CTCs) and tumor-derived Extracellular Vesicles (tdEVs) in predicting overall survival for patients with Castration-Resistant Prostate Cancer (CRPC).
- It involved isolating and counting CTCs and tdEVs in 129 CRPC patients, using established biomarkers to differentiate between favorable and unfavorable prognoses based on overall survival data.
- Results showed that both CTCs and tdEVs, along with other plasma markers, were higher in CRPC patients compared to healthy individuals, with tdEVs providing comparable prognostic information to CTC counts in assessing patient outcomes.
Biomarkers for more precise patient care are needed in metastatic prostate cancer. We have reported a phase II trial (TOPARP-A) of the PARP inhibitor olaparib in metastatic prostate cancer, demonstrating antitumor activity associating with homologous recombination DNA repair defects. We now report targeted and whole-exome sequencing of serial circulating cell-free DNA (cfDNA) samples collected during this trial.
View Article and Find Full Text PDFBackground: Prostate cancer is a heterogeneous disease, but current treatments are not based on molecular stratification. We hypothesized that metastatic, castration-resistant prostate cancers with DNA-repair defects would respond to poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibition with olaparib.
Methods: We conducted a phase 2 trial in which patients with metastatic, castration-resistant prostate cancer were treated with olaparib tablets at a dose of 400 mg twice a day.