Colorectal Cancer Liver Metastases: Genomics and Biomarkers with Focus on Local Therapies

SIMPLE SUMMARY: Colorectal cancer (CRC) is a leading cause of death among cancer patients, and the liver is the most common visceral metastatic site. Despite promising advances in treatment, recurrences with the eventual progression of disease or liver failure are common. Molecular cancer biomarkers are any measurable molecular indicator of the risk of cancer, the occurrence of cancer, or patient outcome, to help personalize treatment and to identify patients who may benefit most from a specific therapy. They may include germline or somatic genetic variants, epigenetic signatures, transcriptional changes, and proteomic signatures. The purpose of this work is to review the utility of tumor genomics and molecular biomarkers associated with colorectal cancer liver metastases (CRLM). As biomarkers have shown great potential for therapeutic decision making, this review would also be valuable for better understanding of CRLM treatment with a focus on local therapies and in particular image-guided liver-directed treatments. ABSTRACT: Molecular cancer biomarkers help personalize treatment, predict oncologic outcomes, and identify patients who can benefit from specific targeted therapies. Colorectal cancer (CRC) is the third-most common cancer, with the liver being the most frequent visceral metastatic site. KRAS, NRAS, BRAF V600E Mutations, DNA Mismatch Repair Deficiency/Microsatellite Instability Status, HER2 Amplification, and NTRK Fusions are NCCN approved and actionable molecular biomarkers for colorectal cancer. Additional biomarkers are also described and can be helpful in different image-guided hepatic directed therapies specifically for CRLM. For example, tumors maintaining the Ki-67 proliferation marker after thermal ablation have been particularly resilient to ablation. Ablation margin was also shown to be an important factor in predicting local recurrence, with a ≥10 mm minimal ablation margin being required to attain local tumor control, especially for patients with mutant KRAS CRLM.