Angle PLC - Assessing risk of brain metastasis in lung cancer
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BREAKTHROUGH RESEARCH HIGHLIGHTS POTENTIAL FOR PARSORTIX TO ASSESS RISK OF BRAIN METASTASIS IN
Potential for early detection of patients at risk of brain metastasis in multiple cancers
Ground-breaking research by Hamburg-Eppendorf demonstrates role of ALCAM expression in lung cancer brain metastasis and shows that this can be measured on CTCs harvested by Parsortix
The study has shown that the ALCAM protein expression on circulating tumor cells (CTCs), harvested by Parsortix, matches the protein expression in brain metastatic tissue biopsies.
This suggests that a Parsortix liquid biopsy blood test may aid in the assessment of the likelihood of a patient suffering a brain metastasis in the future and that the Parsortix blood test may provide additional medical information that could otherwise only be obtained by a highly invasive tissue biopsy of the patient's brain.
ALCAM protein expression is understood to play a role in brain metastasis not only for NSCLC but also for breast and prostate cancers. Brain tissue biopsy procedures are rarely undertaken other than where surgical reduction of the tumor is required treatment, given the associated risks. The ability to investigate aspects of the brain metastasis on a repeat basis during treatment via a simple and cost-effective blood test could fundamentally change the standard of care enabling much more focused therapy decisions in the future.
The new findings are particularly notable for ANGLE because CTCs from brain metastatic patients are generally EpCAM negative, displaying mesenchymal and stem cell traits. These cells cannot be effectively captured by competing CTC systems that are based on antibody-based capture principles, which require EpCAM positive cells.
In the research, which involved 143 NSCLC primary tumors and brain metastases, Hamburg-Eppendorf demonstrated that ALCAM protein expression on the cancer cells assisted progression of the cells through the blood-brain barrier, increased cell adhesion in the brain and helped the cells remain attached under shear stress from blood flow. In a subset of analysed matched pairs of primary tumours and brain metastases, ALCAM protein expression was shown to be induced in brain metastatic tissue compared to primary tumor tissue, indicating a de novo expression of ALCAM in c. 30% of brain metastases. As protein expression of ALCAM on the Parsortix-harvested CTCs correlated with the ALCAM protein expression on the metastatic brain tissue biopsy, a Parsortix liquid biopsy could be used to assess ALCAM protein expression while the primary tissue biopsy cannot.
Lung cancer is the most common cause of new cancer (2.1 million - 11.6%) and cancer-related death (1.8 million - 18.4%) each year (Source: Globocan 2018). Lung cancer is known to spread to the brain in some 40% to 50% of patients in which metastasis has occurred. Up to a third of people with secondary brain cancer will have no symptoms initially and other symptoms can be non-specific and the spread is only found late with imaging systems. The five year survival of NSCLC is only around 15% in developed countries. Patients with brain metastasis have a very poor prognosis with life expectancy usually being under a year and a five year survival rate of only 2.9%. Traditional treatments for brain metastases, such as chemotherapy, are mostly ineffective since they do not cross the blood-brain barrier. Some of the newer targeted therapies or immunotherapies are able to cross the blood-brain barrier but only work in a minority of patients. The researchers believe that ALCAM may be a target for new therapies to reduce brain metastasis and analysis of CTCs may identify potential patient responders.
ANGLE will seek to develop a Parsortix test for ALCAM protein expression on CTCs, which may assist with early identification of risk of brain metastasis. This would facilitate timely treatment and assist pharma companies that may wish to investigate new therapies targeting ALCAM.
The research has been published as a peer-reviewed publication in the
"This new breakthrough research has for the first time demonstrated how ALCAM plays a key role in brain metastasis from lung cancer. The complete correlation between ALCAM protein expression in brain metastasis and circulating tumor cells from a blood test opens the potential for a CTC-based test in the future to assess risk of brain metastasis."
ANGLE Founder and Chief Executive,
"This is tremendous work by the world-class Hamburg-Eppendorf cancer centre. The potential of staining CTCs harvested by Parsortix for ALCAM protein expression provides an excellent opportunity for ANGLE where Parsortix has unique competitive advantages. Brain metastases cannot be accessed for biopsy without highly invasive procedures and a liquid biopsy alternative would be of great benefit to patients to inform treatment."
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Notes for editors
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 and a downstream analysis system for cost effective, highly multiplexed analysis of nucleic acids and proteins.
ANGLE's cell separation technology is called the Parsortix® system, and it enables a liquid biopsy (a simple blood test) to be used to provide the cells of interest 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 types of CTCs as well as CTC clusters in a viable form (alive). CTCs enable the complete picture of a cancer to be seen as being a complete cell they allow DNA, RNA and protein analysis and the live cells harvested can be cultured. The Parsortix technology is the subject of 24 granted patents in
ANGLE's technology for the multiplex evaluation of proteins and nucleic acids of all types is called the HyCEADTM Ziplex® 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 Ziplex 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 (ROC-AUC) 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 30 peer-reviewed publications and numerous publicly available posters, available on our website.
This information is provided by RNS, the news service of the
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