Towards improved Colorectal Cancer Detection and Treatment Monitoring
In this project we aim to exploit long non-coding RNA (lncRNA) biomarkers to improve colorectal cancer (CRC) detection and treatment monitoring. We take on this challenge in a public-private partnership consisting of Cancer Center Amsterdam (CCA) and the Liquid Biopsy Center (LBC), Amsterdam UMC and biomarker company Firalis.
CRC is a leading cause of cancer deaths worldwide. Survival rate for patients with metastatic CRC is less than 20%, while early diagnosis of CRC results in higher chances of cure. Identification of patients that would benefit from adjuvant therapy after surgery is essential to improve personalized treatment of CRC. Therefore, there is an unmet medical need for novel minimally-invasive biomarkers for early-detection and monitoring of therapy efficacy in CRC patients. In the Netherlands, individuals between 55-75 years are screened for CRC using FIT testing. FIT-positive individuals are followed-up with a diagnostic colonoscopy. Unfortunately, ~30% FIT-positives are false positives that have to undergo unnecessary expensive and invasive colonoscopy procedures. Furthermore, it is estimated that ~20% of CRCs are missed with the current approach. For treatment monitoring in CRC, following surgery or systemic therapy, currently a combination of physical exams, CEA measurements and imaging are used. all with limited sensitivity for detection of residual disease or disease progression.
Recently, CCA researchers identified a set of lncRNAs that are specifically expressed in CRC but not in normal tissue or other malignancies. These lncRNAs are secreted in tumor cell derived vesicles, and therefore represent promising biomarkers. In this project, we aim to further identify, develop and validate lncRNA-based biomarkers for early CRC diagnosis and CRC treatment monitoring.
Efforts to uncover circulating cancer-specific lncRNAs yielded a limited success with the current analysis. However, alternative analyses are currently ongoing to improve this outcome. For instance, expansion of the analysis to all detected RNA molecules (coding and non-coding) clearly improve the discovery of potential CRC biomarkers. We hope current ongoing efforts will validate the cancer-specificity of few identified RNA molecules, which may represent potent CRC biomarkers.
