PREDI-LYNCH

The project “Validated non-invasive liquid biopsy tests for cancer PREDIction in LYNCH Syndrome, PREDI-LYNCH" officially starts on 1 May and is funded by the European Commission Horizon Europe Mission on Cancer with 13.6 million Euro.

PREDI-LYNCH will run for six years (2025-2031), and the consortium consists of 28 partners from 16 European countries.

The initiative is led by researcher Mev Dominguez Valentin at the Institute for Cancer Research, Oslo University Hospital (OUH).

The University of Oslo (UiO) and Oslo Cancer Cluster (OCC) are the other two Norwegian partners in the research and innovation project.

Early detection of hereditary cancer

PREDI-LYNCH sets out to make a difference for people with Lynch syndrome (LS) by developing and implementing novel, non-invasive early detection methods for colorectal, endometrial, and urothelial cancers in patients with LS.

The research team addresses an unmet medical need and provides an innovative approach to biomarker discovery for early-stage cancers in LS patients. The consortium gathers leading European researchers, clinicians, biotech companies, and patient advocates. Together they aim to set new standards in early cancer detection for rapid upscaling and to be adopted across EU and globally.

The project has the potential to change clinical practice.

Innovative clinical trial design

The project will use an innovative clinical trial design for evaluating several promising non-invasive liquid biopsy-based technologies in the three most common LS cancer types, to detect cancer at an early stage.

Artificial intelligence (AI) will also be utilized to identify traces of cancer and to ensure that the methods are applicable in different healthcare systems. In addition, socioeconomic and ethical consequences will be assessed to ensure that the solutions are in line with patients' and societal needs and are implementable in different healthcare systems.

The long-term ambition is to offer a multi-omics solution for affordable, accessible, and effective testing to ensure early detection in LS patients.

What Lynch syndrome is

Lynch syndrome is an autosomal dominant cancer syndrome caused by pathogenic germline variants in one of the DNA mismatch repair (MMR) genes.

It is the most common monogenic hereditary cancer predisposition syndrome worldwide.

Carriers of pathogenic MMR variants have a high lifetime risk of developing colorectal (CRC), gynaecological, and urothelial tract cancers as well as gastric, duodenal, small bowel, pancreatic, biliary tract, prostate, kidney, brain, and skin cancers.

LS affects 1 in 440 people of European ancestry. However, many are unaware of their risk, and only 5% of the 2 million estimated LS carriers in Europe are under cancer surveillance.

Tumor-based MMR screening is now routine, which has greatly increased the number of people diagnosed with LS, but this is meaningless without effective means to reduce their cancer risk.

CRC, endometrial, and urothelial cancers are most common in LS. Despite CRC surveillance and aspirin use, up to 60% of LS carriers still develop CRC, and 80% get some form of cancer. Gynaecological surveillance in LS, i.e. transvaginal ultrasound and endometrial biopsy, is invasive and painful, while evidence of benefits is lacking. The studies are of low quality and have contradictory outcomes. Therefore, women are recommended to undergo a hysterectomy in their early forties.

For urothelial cancers, there is no established means of surveillance, meaning that these cancers are often detected at an advanced stage. Uretero-cystoscopy, commonly used for urothelial cancer diagnosis, is invasive and expensive, whereas urinalysis or urine cytology is ineffective. We therefore urgently need to improve cancer surveillance in LS to detect cancers at an early stage, utilizing effective and minimally invasive strategies, to improve patient outcomes and compliance.