International Colorectal Cancer Awareness Month is held in March every year and offers a good opportunity to globally educate as well as promote awareness of the importance of colorectal cancer screening, prevention and treatment.

As the third most common cancer type, colorectal cancer (CRC) is one of the most commonly diagnosed cancers today. With a mortality rate of approximately 50%, it is also one of the leading causes of cancer-related deaths. CRC is an adenocarcinoma that develops in the colon and/or rectum and typically starts as a benign tumor, often in the form of a polyp. A polyp is a small clump of cells formed in the epithelial lining of the intestinal mucosa. Most of the time polyps are harmless, however they can become cancerous with time resulting in a significantly poorer patient prognosis.

Diagnosis is mainly determined based on screening and the golden standard method today is colonoscopy which has poor patient compliance. A colonoscopy is an expensive and invasive method that carries risks of hemorrhage, colonic perforation and cardiorespiratory complications. Another screening method is the guaiac fecal occult blood test (gFOBT) which is based on identification of hemoglobin peroxidase in stool. This is both non-invasive and cost-effective, however it has poor selectivity and sensitivity, leading to a high number of false positives and false negatives. With this being said current screening methods leave much room for improvement.

For treatment prediction, a personalized approach in the form of genetic profiling has been utilized to guide treatment. A good example of this is targeted drug treatments that can antagonize the epidermal growth factor receptor (EGFR) in patients with KRAS-wild-type tumors. EGFR is a transmembrane glycoprotein involved in regulation of cellular proliferation, differentiation, and survival. It is recognized as a key player in CRC initiation and progression and has therefore become a popular therapeutic target in metastatic CRC. KRAS, a protein located downstream of EGFR, is responsible for signal transduction from ligand-bound EGFR to the cell nucleus and is a predictor of resistance to EGFR-targeted therapeutics. Discovering target therapy in this case is crucial for finding adequate chemotherapy for patients with CRC. Despite this, no biomarkers for early diagnosis and detection of CRC exist, and there is an urgent need for non-invasive, cost-effective, specific and sensitive methods of detection. Both urine and blood samples are easily collected, non-invasive as well as cost-effective and are extensively used when screening for novel diagnostic and predictive biomarkers. To this day, several panels of diagnostic biomarkers have been trialed, however none of them have been successfully translated into clinical practice. The reason it failed clinically is most likely due to issues comparing the validation of possible biomarkers in large cohorts to results from currently used screening methods.

To learn more about other proteins, such as EGFR and KRAS, involved in different types of cancers, visit the HPA - Pathology atlas. The underlying data, both on the protein and RNA level, complemented with patient survival data from the TCGA, constitutes an important resource for exploration of novel potential cancer biomarkers. For more specific information about the human proteome in colorectal cancer follow the link - Colorectal cancer proteome.

Anna Maria Clementz