a systems approach to identifying biomarkers
Elypta’s liquid biopsy platform is based on the discovery that a panel of 19 metabolites - glycosaminoglycans (GAGs) - are specifically deregulated across several cancer types. These metabolites participate in a process crucial to cancer progression. Their deregulation depends on the tissue of origin of each cancer, thus allowing the definition of cancer type-specific signatures in blood and urine.
Exceptional accuracy in renal cell carcinoma
Clear cell renal cell carcinoma (ccRCC), the most common form of kidney cancer, is the first indication targeted by Elypta – results to date indicate exceptional accuracy in detecting the disease.
In 2014, it was shown that regulation of metabolism deviated in ccRCC compared to seven other common epithelial tumors (Gatto et al, 2014).
Genome-scale metabolic modeling further elucidated the hubs of metabolic regulation in ccRCC and led to the discovery of a panel of metabolites subject to a strongly coordinated biosynthesis (Gatto et al, 2016 (1)).
In a translational effort to validate this early example of system biomarker, a multicentre discovery cohort of 50 subjects was set up to define a signature for metastatic ccRCC. Remarkable differences were observed between patients and healthy controls. The results were independently validated in a new cohort of 27 subjects. The accuracy of the biomarker ranged from 92.7% up to 100% when blood and urine measurements were combined (Gatto et al, 2016 (1)).
In 2018, a retrospective study on a large American cohort of renal cell carcinoma patients validated previous results and concluded that plasma GAGs are highly sensitive diagnostic and prognostic biomarkers in surgically treated RCC. Notably the test was equally sensitive in early stage (localized) cancer (Gatto et al, 2018).
monitoring the severity of cancer
The quantitative score from the test may be used as a tool to aid prognosis of patients as well as to monitor treatment response. Explorative studies suggest a correlation between Elypta’s test score and the probability of progression or death (Gatto et al, 2016 (2)).
Exploring the potential for a pan-cancer test
Elypta has further investigated metabolic regulation in other cancer types suggesting potential for the system biomarker to be useful in across cancer. Through retrospective studies, distinct signatures has been detected in multiple indications.
Explorative studies are now ongoing in several common cancers to better understand the potential for Elypta’s system biomarker. Meanwhile, prospective trials investigating the utility of clinical applications in renal cell carcinoma are ongoing at Sahlgrenska University Hospital.
Gatto et al, 2014, Proceedings of the National Academy of Sciences, USA
Gatto et al, 2016 (1), Cell Reports
Gatto et al, 2016 (2), Frontiers in Oncology
Jens Nielsen, 2017, Cell Metabolism
Gatto et al, 2018, European Urology Oncology