The genomics of liver metastases from colon and rectal cancer: An Invited Commentary (invitation from Lee Ocuin, MD and Kevin Behrns, MD) for the special issue of “Management of Advanced Primary and Secondary Liver Malignancies”

Over the past two decades, the treatment of patients with cancer has become increasingly structured around the identification of cancer mutations genetically driving the disease. Upfront knowledge of these data has implications for both the selection and omission of certain cytotoxic and targeted therapies. For patients with colon or rectal cancer metastatic to the liver, next-generation sequencing to identify these key mutational drivers should be done at the outset of diagnosis to understand the full spectrum of treatment options available to a patient. Mutational profiling for patients with colorectal liver metastasis initially led to the recognition of treatment resistance to epidermal growth factor inhibitors in patients with a KRAS mutation and now has expanded to include other targeted options. As the treatment options for patients with colorectal liver metastasis continue to evolve, it is increasingly important to integrate genomic data into selecting patients who will benefit from hepatic resection, ablative techniques, and liver-directed therapy. Herein, we review the most common mutations encountered in treating patients with colorectal liver metastasis, focusing specifically on epidermal growth factor receptor, KRAS/NRAS, BRAF, and the mismatch repair pathway with resultant implications to the medical and surgical treatment for these patients.