Exploiting the peculiarity of Cancer Cells and Exosome Biology for Multi-Cancer Early Detection

“By developing effective strategies to identify cancer early, lives can be saved and the personal, societal and economic costs of cancer care are reduced.” World Health Organization

Cancer is set to become the dominant cause of death globally by the middle of this century.
This forecast is, to a great extent, a consequence of mankind’s success in improving global longevity resulting in an 
increasingly ageing global population. As cancer is a consequence of longevity in a multi-cellular organism, cancer 
incidence is inexorably increasing.

The history of our battle against cancer has been dominated by the improved understanding of the fundamental biological 
processes underlying uncontrolled cell growth (‘cancer’) while improving treatments, both surgical and pharmacological, for 
the disease. These advanced treatments are typically targeted at late-stage cancers because this is when the majority of 
people are diagnosed with the disease. Despite the success and wide availability of screening programs for cancer, over 
60% of cancers are identified at late stages (Stage III or IV) and yet the chance of surviving cancer improves significantly if 
cancer is detected at an earlier stage. Additionally, only a handful of the most prevalent cancers have routine screening programs in place in most countries, and 
so the majority of the most pernicious cancers have no method of reliable diagnosis.

How would this pandemic explosion of cancer incidence be slowed or even stopped if all cancers could be detected 
quickly and cheaply at their earliest, detectable stage?

How would people’s lives be improved if, with the simplicity of a single blood sample, they had the reassurance to be 
cancer-free or the confidence of a successful outcome if found to have an early cancerous lesion?

This is the promise of ‘liquid biopsy’ for early cancer detection and Rivela is exploiting the biology of exosomes to make 
this a reality.

Today, cancer screening is offered through single cancer screening solutions for only a few of the commonest, tractable, cancers, while 70% of cancers do not have any screening program in place. These single cancer screening programs are uneconomic and suffer from low compliance at population scale.

Multi-Cancer Early-Detection (MCED) approaches aim to increase cancer detection rates in populations, and increase the compliance and overall personal, societal and economic impact on healthcare.

Despite numerous current high profile Governmental, Industry and Health System initiatives, today there is no truly effective MCED solution, either clinically or economically. The incumbent solutions offered by competitors are predominantly based on complex, Next Generation Sequencing, AI-based tests, that cannot deliver on clinical performance in early screening setting, nor are scalable and affordable for implementation at general population level.

Rivela’s approach is built on the expertise and scientific research of our parent company, ‘Exosomics SpA’, who for over a decade have pioneered the understanding, characterisation, and molecular engineering of exosomes for diagnostic and therapeutic applications. Our IP-protected technology has already demonstrated that it distinguishes Early Stage 1 cancers from late-stage, using analytical techniques that are cost-effective and widespread in diagnostic laboratories in most countries.

When searching for the proverbial needle in the haystack, Rivela’s technology both reduces the size of the ‘haystack’ and uses a ‘biological magnet’ to specifically find the ‘cancer needle’.

This combined approach delivers the best clinical performance without the need for expensive and complex Next-Generation Sequencing laboratories.

Step 1 – Start with the Best Sample

We start with optimized, proprietary methods to efficiently separate the plasma fraction of the blood sample that contains exosomes.

This step ensures sample-to-sample reproducibility and exosome integrity and also enables sensitive downstream analysis by reducing blood components that may interfere with the test.

Step 2 – Make the Search Easier

We then specifically enrich for tumour-derived exosomes resulting in a cleaner, concentrated sample, less prone to interference from other blood constituents. This enrichment, which is not feasible in other liquid biopsy approaches, ensures that the downstream analytical testing can be achieved using standard laboratory immunoassay and qPCR equipment and processes.

Step 3 – Measure the Right Thing

Rivela then analyses the enriched sample using proprietary markers that are indicative of ALL cancers, based on well-defined ‘hallmarks of cancer’ – biological changes that all cells undergo to become cancerous. This analysis uses both molecular and proteomics signatures, increasing the performance of the final result

Since the initial concept of liquid biopsy as an alternative, non-invasive replacement for traditional tissue biopsy was proposed, the leading approaches to early tumour detection via liquid biopsy have been based on the analysis of circulating tumor DNA (ctDNA)

Rivela’s focus on using exosomes as the vehicles for universal cancer biomarkers significantly out-performs these approaches because,

    1. Exosomes are produced and detectable at the earliest stages of tumor establishment, unlike ctDNA

    2. Tumor-derived exosomes can be enriched, thereby reducing the considerable analytical sensitivity challenge faced by ctDNA methods

    3. Exosomes carry different classes of analyte – nucleic acid, proteins, small molecular metabolites – permitting a broad spectrum diagnostic approach to identifying cancer compared to a reliance on nucleic acids only

These features lead to superior clinical performance compared to ctDNA-based competitors.