Metastatic colorectal cancer: mechanisms and emerging therapeutics

Metastatic colorectal cancer (mCRC) remains a lethal disease with an approxi-mately 14% 5-year survival rate. While early-stage colorectal cancer (CRC) can be cured by surgery with or without adjuvant chemotherapy, mCRC cannot be eradicated due to a large burden of disseminated cancer cells comprising ther-apy-resistant metastasis-competent cells. To address this gap, recent studies have focused on further elucidating the molecular mechanisms underlying colo-rectal metastasis and recognizing the limitations of available therapeutic interven-tions. In this review, we discuss newfound factors that regulate CRC cell dissemination and colonization of distant organs, such as genetic mutations, identification of metastasis-initiating cells (MICs), epithelial-mesenchymal transi-tion (EMT), and the tumor microenvironment (TME). We also review current treat-ments for mCRC, therapeutic regimens undergoing clinical trials, and trending preclinical studies being investigated to target treatment-resistant mCRC.