Angle PLC Announces Spread of Breast Cancer Accelerates During Sleep


CTCs, CTC clusters and CTC-WBC clusters harvested using Parsortix were more numerous and more aggressive in initiating metastasis during sleep

Potential for optimisation of cancer care by utilising the Parsortix system in time-controlled approaches for treatment

GUILDFORD, SURREY / ACCESSWIRE / June 27, 2022 / ANGLE plc (AIM:AGL OTCQX:ANPCY), a world-leading liquid biopsy company, is delighted to announce ground-breaking research by the world-class team at the Molecular Oncology Laboratory at the Swiss Federal Institute of Technology (ETH) Zurich, Switzerland. The study utilised the Parsortix® system to investigate the impact of sleep on the release of CTCs in preclinical models and 30 patients with breast cancer (21 with early stage and 9 with metastatic disease).

The Parsortix system provided biomarker-independent isolation and harvest of CTCs, CTC clusters and CTC-white blood cell (WBC) clusters. This was crucial in enabling the researchers to develop a new understanding of cancer metastasis with the discovery that the release of CTCs, CTC clusters and CTC-WBC clusters is highly dependent on the circadian rhythm with far greater metastatic activity during the rest phase (i.e. during the night). Not only are more CTCs, CTC clusters and CTC-WBC clusters released during the rest phase, but gene expression analysis (RNA sequencing) found that genes relating to cell division and metastatic potential were consistently upregulated, leading to more aggressive cancer cells.

These findings provide novel insight into the role of the circadian rhythm in the generation of CTCs with metastatic potential. This research could allow for the optimisation of cancer care by utilising time-controlled approaches for the treatment of breast cancer. For example, treatments which are most effective during the rest-phase, or which can reduce the impact of the circadian rhythm on CTC and CTC cluster release during the rest phase. The research also identified the role of key circadian rhythm hormones in metastasis including melatonin, testosterone and glucocorticoids, which may provide targets for novel drug therapies and are likely to be of interest for investigation by biopharma companies.

Breast cancer is the leading cause of cancer in women. In 2022, it is estimated that c.290,000 women will be diagnosed with breast cancer and further c.3.8 million women are living with or after breast cancer in the US. Globally, the number of new breast cancer cases diagnosed each year is expected to increase by more than a third, and the number of deaths each year is expected to increase by more than 50% by 2040.

Professor Nicola Aceto, ETH Zurich, commented:

"We have worked with the Parsortix system for over four years now. The ability to reliably harvest CTCs, CTC clusters and CTC-WBC clusters has allowed us to develop an understanding of cancer metastasis not previously possible. In this study we observed a striking and unexpected pattern of CTC generation dynamics in both patients with breast cancer and preclinical models, highlighting that most spontaneous CTC intravasation events occur during sleep. Further, we demonstrate that rest-phase CTCs are highly prone to metastasize, whereas CTCs generated during the active phase are devoid of metastatic ability. These findings suggest the need for time-controlled approaches for the characterisation and treatment of breast cancer and the investigation of new drug targets."

ANGLE Founder and Chief Executive, Andrew Newland, added:

"We are delighted to report on this ground-breaking research which furthers the understanding of the metastatic process. Metastasis is responsible for 90% of cancer patient deaths so these findings mark a significant development in the understanding of cancer progression and provide novel insight for drug discovery. This study highlights the capabilities of the Parsortix system to harvest CTC clusters and CTC-WBC clusters, which are key to understanding the tumour microenvironment and immune system interaction and evasion. Pharma companies in discussion with ANGLE are showing increasing interest in investigating not only CTCs but also the associated immune cells (WBC) particularly when both cell types are found in the same cluster."

The research has been published as a peer-reviewed publication in the high-impact Journal Nature and is available online at

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Notes for editors

About ANGLE plc

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 63 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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