About the disease

Briefly about the disease and its targeted therapies

Most colorectal cancers (CRC) start as an overgrowth in the mucosal layer, forming a benign polyp. This, due to further acquired genetic changes, becomes malignant over time, that is why it has to be removed and examined for any possible sign of malignant transformation.  In a minority of the cases, however, CRC begins immediately as an invasive cancer without the formation of polyps.  

About 75% of the CRC patients display the sporadic disease with no apparent evidence of having inherited the disorder. The remaining 10% to 30% of the patients have a family history of CRC, which suggests hereditary contribution, common exposure, or shared risk factors among family members or a combination of these. Hereditary CRC has two well-described forms. The first is polyposis (including familial adenomatous polyposis (FAP) and attenuated FAP (AFAP), which are caused by pathogenic variants in the APC gene, and MUTYH-associated polyposis, which is caused by pathogenic variants in the MUTYH gene); the second form is the Lynch syndrome (often referred to as hereditary nonpolyposis colorectal cancer), which is caused by germline pathogenic variants in DNA MMR genes (MLH1, MSH2, MSH6, and PMS2) and EPCAM. Other CRC syndromes and their associated genes include oligopolyposis (POLE, POLD1), NTHL1, juvenile polyposis syndrome (BMPR1A, SMAD4), Cowden syndrome (PTEN), and Peutz-Jeghers syndrome (STK11).

In metastatic colon cancer cases, NCCN experts recommend testing for KRAS and NRAS mutations because some targeted treatments are not effective if these genes are abnormal. Out of every 100 metastatic colon cancer patients, about 5 to 9 have mutations in the BRAF gene enabling targeted therapy.