The structure and function relationship is further demonstrated in a tumor's mutational status. In colorectal cancer, mutational analysis, including tests for
KRAS,
NRAS, and
BRAF mutations and MSI-high tumors, has enabled personalized therapy beyond standard TNM staging–based therapy.
14 Researchers are able to tailor treatments to maximize efficacy as the understanding of both somatic and germline mutations improves. For example, patients with resected colorectal liver metastasis harboring a
KRAS mutation were found to have a significantly worse 3-year recurrence-free survival after adjuvant hepatic artery infusion plus systemic therapy than patients with
KRAS wild-type mutations.
15 Additionally, the epidermal growth factor receptor, or EGFR, antagonist cetuximab has been shown to provide no survival advantage in patients with a
KRAS mutation.
16 On the other hand, patients with solid organ MSI-high tumors have shown a greater response to immune checkpoint inhibitors, specifically nivolumab.
17 Therefore, by understanding the differences in tumor mutational status, therapies can be directed toward the individual patient rather than the disease. This approach can save patients from unnecessary procedures and therapies, which all carry risk. Furthermore, as researchers and physicians better understand a patient's genetic structure, treatment can be tailored to fit a genetic phenotype. For example, a germline
BRCA mutation is known to confer a high risk of breast as well as ovarian cancer in woman. As the genetic structure of
BRCA is altered, there is a loss of function of tumor suppression, leading to an increased risk of cancer. As a result, prophylactic surgery is routinely recommended to decrease the risk of cancer.
18,19