ORCID Profile
0000-0002-7380-1170
Current Organisations
UNSW Faculty of Medicine
,
University of Sydney
,
Royal Australasian College of Physicians
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: MDPI AG
Date: 08-07-2019
DOI: 10.3390/CELLS8070688
Abstract: Detection of androgen receptor (AR) variant 7 (AR-V7) is emerging as a clinically important biomarker in castrate resistant prostate cancer (CRPC). Detection is possible from tumor tissue, which is often inaccessible in the advanced disease setting. With recent progress in detecting AR-V7 in circulating tumor cells (CTCs), circulating tumor RNA (ctRNA) and exosomes from prostate cancer patients, liquid biopsies have emerged as an alternative to tumor biopsy. Therefore, it is important to clarify whether these approaches differ in sensitivity in order to achieve the best possible biomarker characterization for the patient. In this study, blood s les from 44 prostate cancer patients were processed for CTCs and ctRNA with subsequent AR-V7 testing, while exosomal RNA was isolated from 16 s les and tested. Detection of AR and AR-V7 was performed using a highly sensitive droplet digital PCR-based assay. AR and AR-V7 RNA were detectable in CTCs, ctRNA and exosome s les. AR-V7 detection from CTCs showed higher sensitivity and has proven specificity compared to detection from ctRNA and exosomes. Considering that CTCs are almost always present in the advanced prostate cancer setting, CTC s les should be considered the liquid biopsy of choice for the detection of this clinically important biomarker.
Publisher: MDPI AG
Date: 25-03-2022
Abstract: Immunotherapy (IO), involving the use of immune checkpoint inhibition, achieves improved response-rates and significant disease-free survival for some cancer patients. Despite these beneficial effects, there is poor predictability of response and substantial rates of innate or acquired resistance, resulting in heterogeneous responses among patients. In addition, patients can develop life-threatening adverse events, and while these generally occur in patients that also show a tumor response, these outcomes are not always congruent. Therefore, predicting a response to IO is of paramount importance. Traditionally, tumor tissue analysis has been used for this purpose. However, minimally invasive liquid biopsies that monitor changes in blood or other bodily fluid markers are emerging as a promising cost-effective alternative. Traditional biomarkers have limitations mainly due to difficulty in repeatedly obtaining tumor tissue confounded also by the spatial and temporal heterogeneity of tumours. Liquid biopsy has the potential to circumvent tumor heterogeneity and to help identifying patients who may respond to IO, to monitor the treatment dynamically, as well as to unravel the mechanisms of relapse. We present here a review of the current status of molecular markers for the prediction and monitoring of IO response, focusing on the detection of these markers in liquid biopsies. With the emerging improvements in the field of liquid biopsy, this approach has the capacity to identify IO-eligible patients and provide clinically relevant information to assist with their ongoing disease management.
Publisher: Informa UK Limited
Date: 29-08-2020
Publisher: MDPI AG
Date: 11-05-2020
DOI: 10.3390/APP10093338
Abstract: Glioblastoma (GBM) is the most common form of primary brain cancer in adults and tissue biopsies for diagnostic purposes are often inaccessible. The postulated idea that brain cancer cells cannot pass the blood–brain barrier to form circulating tumor cells (CTCs) has recently been overthrown and CTCs have been detected in the blood of GBM patients albeit in low numbers. Given the potential of CTCs to be analyzed for GBM biomarkers that may guide therapy decisions it is important to define methods to better isolate these cells. Here, we determined markers for immunomagnetic targeting and isolation of GBM-CTCs and confirmed their utility for CTC isolation from GBM patient blood s les. Further, we identified a new marker to distinguish isolated GBM-CTCs from residual lymphocytes.
Publisher: Springer Science and Business Media LLC
Date: 25-10-2023
Publisher: MDPI AG
Date: 04-01-2022
DOI: 10.3390/JCM11010257
Abstract: Androgen Receptor (AR) alterations ( lification, point mutations, and splice variants) are master players in metastatic castration resistant prostate cancer (CRPC) progression and central therapeutic targets for patient management. Here, we have developed two multiplexed droplet digital PCR (ddPCR) assays to detect AR copy number (CN) and the key point mutation T877A. Overcoming challenges of determining gene lification from liquid biopsies, these assays cross-validate each other to produce reliable AR lification and mutation data from plasma cell free DNA (cfDNA) of advanced prostate cancer (PC) patients. Analyzing a mixed PC patient cohort consisting of CRPC and hormone sensitive prostate cancer (HSPC) patients showed that 19% (9/47) patients had AR CN lification. As expected, only CRPC patients were positive for AR lification, while interestingly the T877A mutation was identified in two patients still considered HSPC at the time. The ddPCR based analysis of AR alterations in cfDNA is highly economic, feasible, and informative to provide biomarker detection that may help to decide on the best follow-up therapy for CRPC patients.
No related grants have been discovered for Paul de Souza.