The purpose of precision cancer medicine is not to categorize or classify cancers solely by site of origin, but to define the genomic alterations in the cancer’s DNA that are driving that specific cancer. Precision cancer medicine utilizes molecular diagnostic testing, including DNA sequencing, to identify cancer-driving abnormalities in a cancer’s genome. Once a genetic abnormality is identified, a specific targeted therapy can be designed to attack a specific mutation or other cancer-related change in the DNA programming of the cancer cells. Precision cancer medicine uses targeted drugs and immunotherapies engineered to directly attack the cancer cells with specific abnormalities, leaving normal cells largely unharmed.
By testing an individual’s colon cancer for specific unique biomarkers, doctors can offer the most personalized treatment approach utilizing precision medicines.
Colorectal Cancer Biomarkers That Can Be Targeted
The RAS Genes: KRAS and NRAS KRAS and NRAS genes play an important role in instructing colorectal cancer cells to grow and divide as part of the epidermal growth factor receptor (EGFR) process. If your cancer has a KRAS or NRAS mutation, drugs that target EGFR (like cetuximab, and panitumumab) may not benefit you. “Wild type” means you do not have the mutation and the drugs may provide some benefit. All patients with advanced colon cancer should undergo RAS biomarker testing before beginning treatment.
BRAF: BRAF is also a gene that signals cells to divide. Patients with mutant BRAF genes generally have a poorer prognosis (chance of survival and worse side effects). BRAF testing is generally done at the same time as RAS testing.
PIK3CA: While somewhat new, a growing number of clinicians are testing for mutant PIK3CA genes; particularly in patients who have early-stage colorectal cancer. There is some suggestion that aspirin use may help decrease the risk of recurrent colorectal cancer in patients with early stage disease and PIK3CA mutation.
Microsatellite Instability High (MSI-H): MSI-H is a DNA abnormality found in about 15% of colon cancers. It is most often found in tumors associated with genetic syndromes like Lynch syndrome but can also occur sporadically. MSI-H is what “happens” when the genes that regulate DNA function don’t work correctly. These DNA regulating genes, known as Mismatch Repair Genes (MMR), work like genetic “spell checkers.” When problems occur in these spell-checking MMR genes, it means that areas of DNA start to become unstable. A high frequency of instability is called MSI-H. Patients with MSI-H tumors may respond differently to certain treatments. It is important to test colon cancers for this trait because it can help determine if the colorectal cancer is related to an inherited family syndrome.
Carcinoembryonic Antigen (CEA): CEA is a protein that may be higher in colorectal cancer patients. High levels of CEA may indicate that cancer is present or a treatment is not working. Low levels may indicate that the body is responding to a treatment.