Local, intestinal biomarkers for early detection of colorectal cancer

University essay from Uppsala universitet/Institutionen för farmaci

Abstract: Colorectal cancer (CRC) is one of the deadliest cancers in the world. The early stage of the disease is usually asymptomatic and therefore screening methods for colorectal cancer need to improve. There is a need for early detection of CRC as treatment is less effective in the advanced stage of the disease.  The current standard screening methods are endoscopy and fecal immunochemical blood tests. Endoscopy is a commonly used method to diagnose the patient, but it is costly, time consuming, and rather unpopular for the patients. An alternative could be to develop targeted molecular imaging probes that specifically deliver agents for example magnetic resonance imaging to colon adenomas and adenocarcinomas. This alternative would be non-invasive and able to detect the disease before morphological changes become evident. Biomarkers are used as an objective indicator of an altered biological process. Here, a literature study was conducted to identify protein biomarkers that are overexpressed in early stages of CRC. This study has focused on biomarkers that could be used to target imaging agents to cancerous lesions. Thus, the biomarkers need to be membrane-bound and expressed on the luminal side of the gastrointestinal tract. This will help future research to develop orally administered targeted imaging probes. Furthermore, a smaller literature search was conducted to identify cell and mouse models representing early stages of CRC. This was done to facilitate translational research going from in vitro to in vivo. Ideally the same protein is available in cell lines, mouse models and humans to enable translational research. This work has resulted in the selection of 7 different proteins that are upregulated during early stages of CRC. These proteins are potentially apically located and therefore possible targets for monoclonal antibodies. These findings might lead to a novel way for preventive patient screening and hopefully reduce the mortality for colorectal cancer.

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