Prostate cancer cells may use invasive cellular protrusions to aid entry into the blood stream, a potential target in the metastatic process for novel therapy development
Parsortix system isolates CTCs in 94% of prostate cancer patients, showing some association with matrix degradation and invasive cellular protrusion formation
GUILDFORD, UK / ACCESSWIRE / June 14, 2022 / ANGLE plc (AIM:AGL) (OTCQX:ANPCY), a world-leading liquid biopsy company, is pleased to announce that researchers at King's College London, UK, have published data investigating the role of invasive cellular protrusion, known as invadopodia, activity in prostate cancer, and a potential role in the formation of circulating tumour cells (CTCs). This novel finding has the potential to provide a new target, within the metastatic process, for the development of novel therapeutics in the prostate cancer setting.
Invasive cellular protrusions are thought to be involved in degradation of the extracellular matrix (ECM), driving tumour invasion and metastasis. Formation of invasive cellular protrusions has been seen in many metastatic cancer cell lines, but there has previously been little evidence in prostate cancer cell lines. Firstly, the authors of this study have identified prostate cancer cell lines that form spontaneous invasive cellular protrusions in vitro, and show metastatic behaviour in vivo, proving to be a valid model for future studies.
In addition, the researchers used ANGLE's marker-independent Parsortix® system to isolate CTCs from prostate cancer patients with a Gleason score ≥7 (medium to high grade cancer). CTCs were identified in 16 out of 17 patients, with 8 patients having 10 or more CTCs. Overall, 75% of patients showed evidence of ECM degradation near the CTCs, and 40% of patients had invasive cellular protrusion presence aligning with ECM degradation. The authors speculate that prostate cancer cells detaching from the primary tumour may use the invasive cellular protrusions to aid entry into the blood stream. There is the potential for novel therapy development targeting this step in the metastatic process.
The Parsortix system's ability to effectively isolate CTCs from the blood of prostate cancer patients may allow novel therapeutic development targeting the mechanisms of invadopodia and reducing metastatic spread of the cancer.
Prostate cancer is the most common cancer in men. The American Cancer Society estimates that there will be 268,490 new cases in the US in 2022. For localised disease the 5-year relative survival is 100%, this drops to only 30.6% when the cancer has metastasised, suggesting a need for better targeted treatment that could prevent the early stages of metastasis, improving survival for prostate cancer patients.
Professor Claire Wells, School of Cancer and Pharmaceutical Sciences, King's College London, commented: "We have found that prostate cancer CTCs form invadopodia structures and are intrinsically capable of degrading the matrix; our novel finding paves the way for a new series of studies. Our study supports further exploration of invadopodia activity in the prostate cancer setting with the potential to develop novel therapeutics."
ANGLE Founder and Chief Executive, Andrew Newland, added: "We are pleased to report on the use of the Parsortix system for the unbiased isolation of CTCs in prostate cancer, revealing a potentially novel understanding of prostate cancer CTC formation. This research suggests a potential for the development of novel therapeutics targeting the early stages of prostate cancer metastasis, which is important for improving patient survival."
About ANGLE plcwww.angleplc.com ANGLE is a world leading liquid biopsy company with sample-to-answer solutions. ANGLE's proven patent protected platforms include a circulating tumor cell (CTC) harvesting technology known as the Parsortix® system and a downstream analysis system for cost effective, highly multiplexed analysis of nucleic acids and proteins.
ANGLE's Parsortix® system is FDA cleared for its intended use in metastatic breast cancer and is currently the first and only FDA cleared medical device to harvest intact circulating cancer cells from blood.
Intended use The Parsortix® PC1 system is an in vitro diagnostic device intended to enrich circulating tumor cells (CTCs) from peripheral blood collected in K2EDTA tubes from patients diagnosed with metastatic breast cancer. The system employs a microfluidic chamber (a Parsortix cell separation cassette) to capture cells of a certain size and deformability from the population of cells present in blood. The cells retained in the cassette are harvested by the Parsortix PC1 system for use in subsequent downstream assays. The end user is responsible for the validation of any downstream assay. The standalone device, as indicated, does not identify, enumerate or characterize CTCs and cannot be used to make any diagnostic/prognostic claims for CTCs, including monitoring indications or as an aid in any disease management and/or treatment decisions.
The Parsortix system enables a liquid biopsy (a simple blood test) to be used to provide the circulating metastatic breast cancer cells to the user in a format suitable for multiple types of downstream analyses. The system is based on a microfluidic device that captures cells based on a combination of their size and compressibility. The system is epitope independent and can capture all phenotypes of CTCs (epithelial, mesenchymal and EMTing CTCs) as well as CTC clusters in a viable form (alive). CTCs harvested from the system enable a complete picture of a cancer to be seen; as being an intact cell they allow DNA, RNA and protein analysis as well as cytological and morphological examination and may provide comparable analysis to a tissue biopsy in metastatic breast cancer. Because CTC analysis is a non-invasive process, unlike tissue biopsy, it can be repeated as often as needed. This is important because cancer develops and changes over time and there is a clear medical need for up-to-date information on the status of a patient's tumor. In addition, the live CTCs harvested by the Parsortix system can be cultured, which offers the potential for testing tumor response to drugs outside the patient.
The Parsortix technology is the subject of 26 granted patents in Europe, the United States, China, Australia, Canada, India, Japan and Mexico with three extensive families of patents are being progressed worldwide.
In the United States, the Parsortix® PC1 system has received a Class II Classification from FDA for use with metastatic breast cancer patients. FDA clearance is seen as the global gold standard. ANGLE's Parsortix system is the first ever FDA cleared system for harvesting CTCs for subsequent analysis. ANGLE has applied the IVD CE Mark to the same system for the same intended use in Europe.
ANGLE has also completed two separate 200 subject clinical studies under a program designed to develop an ovarian cancer pelvic mass triage test, with the results showing best in class accuracy (AUC-ROC) of 95.1%. The pelvic mass triage assay has undergone further refinement and optimisation and a 200 patient clinical verification study has now completed enrolment.
ANGLE's technology for the multiplex evaluation of proteins and nucleic acids of all types is called the HyCEADTM platform and is based on a patented flow through array technology. It provides for low cost, highly multiplexed, rapid and sensitive capture of targets from a wide variety of sample types. A proprietary chemistry approach (the HyCEAD method) allows for the capture and amplification of over 100 biomarkers simultaneously in a single reaction. The HyCEAD system is extremely sensitive and is ideal for measuring gene expression and other markers directly from Parsortix harvests and was used in the ovarian cancer pelvic mass triage test to achieve best in class accuracy (AUC-ROC) of 95.1%.
ANGLE's proprietary technologies can be combined to provide automated, sample-to-answer results in both centralised laboratory and point-of-use cartridge formats.
ANGLE has established formal collaborations with world-class cancer centres and major corporates such as Abbott, Philips and QIAGEN, and works closely with leading CTC translational research customers. These Key Opinion Leaders (KOLs) are working to identify applications with medical utility (clear benefit to patients), and to secure clinical data that demonstrates that utility in patient studies. The body of evidence as to the benefits of the Parsortix system is growing rapidly from our own clinical studies in metastatic breast cancer and ovarian cancer and also from KOLs with 61 peer-reviewed publications and numerous publicly available posters from 31 independent cancer centres, available on our website.
ANGLE has established clinical services laboratories in the UK and the United States to accelerate commercialisation of the Parsortix system and act as demonstrators to support product development. The laboratories offer services globally to pharmaceutical and biotech customers for use of Parsortix in cancer drug trials and, once the laboratories are accredited and tests validated, will provide Laboratory Developed Tests (LDTs) for patient management.
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