Emerging paradigms in the treatment of liver metastases in colorectal cancer.

Efforts to combat colorectal cancer have benefited from improved screening and surveillance, which facilitates early detection. The survival rate associated with diagnosis at stage I is approximately 90%. However, progress in improving survival in metastatic colorectal cancer (mCRC) has been minimal. This review focuses on mCRC with special emphasis on the molecular aspects of liver metastases, which is one of the most frequently involved organ site. Better molecular evidence is required to guide the decisions for surgical and other interventions used in the clinical management of mCRC. Results from different treatment modalities have exposed significant gaps in the existing paradigms of the mCRC management. Indeed there is a critical need to better understand molecular events and pathways that lead to colorectal cancer liver metastasis. Such a focused approach may help identify biomarkers and drug targets that can be useful in the clinical applications. With this focus, we provide an account of the molecular pathways involved in the spread of CRC to the liver. Specifically, the molecular changes at the DNA and RNA levels that are associated with liver metastases are discussed. Similarly, we describe relevant microRNAs that are identified as regulators of gene expression and can also serve as biomarkers. Conventionally applied biomarkers are not yet specific and sensitive enough to be relied in routine clinical decision making. Hence search for novel biomarkers is critically needed especially if these can be utilized using liquid biopsies. This review provides a comprehensive analysis of current molecular evidence along with potential future directions that could reshape the diagnostic and management paradigms and thus mitigate the devastating impact of colorectal cancer metastasis to the liver.