Colorectal cancer is the third most diagnosed cancer, with 1.4 million new cases worldwide in 2012. In the United States alone in 2014, an estimated 136,830 new cases will be diagnosed, and about 50,310 deaths will result from the disease. Ninety percent of patients survive if diagnosed during the localized stage of colorectal cancer (5-year survival rate), but only 40% of colorectal cancer cases are diagnosed at this stage. Enhancing early detection is therefore critical to increasing survival. The current standard of care to detect colorectal cancer is the colonoscopy, which uses white light to identify lesions, polyps, and abnormalities visually by their shape. Unfortunately, this method fails to detect over one in five polyps because many of the polyps are flat or indented in the lining of the colon. A new method for detection of colorectal cancer facilitates more effective screening by highlighting pre-cancerous and cancerous tissue.
Claudin-1-specific peptides as biomarkers for colorectal cancer diagnosis
Claudin-1 is elevated in cancer in a variety of tissues, most prominently in colorectal cancer and in cancer formation associated with ulcerative colitis/inflammatory bowel disease. Claudin-1 can therefore be used as an identifier for pre-cancerous and cancerous lesions in the colon and rectum. Phage display and standard molecular biology techniques have identified peptides that bind specifically to claudin-1. The specificity of these peptides was confirmed with confocal microscopy and stereomicroscopy in pre-malignant human colon tissue and with wide-field endoscopy and dual-axes confocal endomicroscopy in vivo. These peptides can be connected to fluorophores (optical labels or dyes) and serve as biomarkers for tissue with high claudin-1 expression. Physicians would use a fluorescent microscope that fits into a standard endoscope to see these labels and locate pre-cancerous and cancerous tissue, guiding biopsies and surgical removal, if necessary.
Peptides themselves are inexpensive to produce in large quantities and they have rapid binding properties with high specificity, allowing for low-cost, fast, and accurate diagnoses. They can be applied topically in high concentrations to the digestive tract, which maximizes binding interactions and achieves optimal image contrast with minimal risk for toxicity. In addition, the small size of the peptides’ short amino acid sequences promotes deep tissue penetration and minimizes the chances of evoking a response by the body’s immune system. With this peptide-based technology, physicians can use molecular targets rather than only morphological changes to find pre-cancerous and cancerous tissue. All of these benefits promote earlier, more precise diagnoses and greater reliability. This reduces discomfort and cost over a patient’s lifetime by decreasing the need for extra colonoscopies and increasing the amount of time between exams.
- Diagnostic for colorectal cancer
- Uses molecular targets to identify pre-cancerous and cancerous tissue, rather than structural changes
- Inexpensive production
- Rapid, highly-specific binding
- Minimal risk of toxicity or immunogenicity