Predictive biomarkers for Colorectal Cancer Recurrence
CRC is a heterogeneous disease and post-surgical recurrence occurs in 30 to 50 percent of cases. Current monitoring of recurrence is via a blood test for carcinoembryonic antigen (CEA) in combination with CT scans and other clinical assessments. Unfortunately, these surveillance methods detect fewer than half of the recurrences in time to allow for resection surgery with curative intent. However, detecting recurrent CRC in early asymptomatic stages will reduce intensive treatment needs and associated costs, and improve survival rates. In addition, chemotherapy is associated with significant morbidity and costs, but there is no means of identifying those at high risk who might benefit from chemotherapy, nor who are unlikely to progress or those will not respond, and therefore could be spared treatment. These factors highlight the need for improved signatures of risk of CRC recurrence after primary treatment.
A. DNA Methylation biomarkers
In collaboration with WEHI, a panel of DNA methylation biomarkers will provide a signature of risk of recurrence of colorectal cancer after primary treatment. This will allow targeting of more aggressive treatment and monitoring to those most at risk (saving lives), while sparing those at low risk of unnecessary treatment regimes.
B. Prognostic protein markers
A collaboration with SA Health, Lyell McEwin Hospital and Walter and Eliza Hall Institute
Currently CEA, or carcinoembryonic antigen, is the only non-invasive marker used clinically to monitor patients already diagnosed with stage 1 to 4 colorectal cancer. CEA is a protein detected in the blood of patients. Serial measurements (i.e., measurements taken over time) can be used as an indicator of disease recurrence, and high levels of CEA correlates with poor patient outcome. Although widely used, this marker will only detect recurrence in a subset of patients. This means that for many patients, disease recurrence will not be detected until it is too late.
We have identified a panel of protein markers in blood that appears to be better than CEA at detecting recurrence of disease, and that may be able to better predict patient outcome. We are currently testing this panel of proteins in a cohort of colorectal cancer patients.
C. Identifying markers of polyps and adenomas, precursors of colorectal cancer
This project is in collaboration with SA Pathology and Lyell McEwin Hospital
Currently, we are analysing -omics data from patients diagnosed with different subtypes of colorectal cancer, including those with the BRAF V600E mutation and lateral spreading tumours. There is evidence to indicate that these subtypes have a different clinical course and do not respond to standard treatment regimes. Also, not all polyps or adenomas progress to cancer.
In addition to identifying markers that differentiate between these subtypes (i.e., diagnostic markers), utilising the organoid platform and analysis of -omics data will allow us to better understand the biology of the disease and determine why some early stage lesions (polyps and adenomas) become cancerous.