Radical surgery currently represents the only treatment with curative potential for patients with
colorectal cancer (CRC) liver
metastases. Unfortunately, only a minority of cases is eligible for hepatic resection and many patients still develop recurrent disease, which underscores the need for more effective adjuvant treatments. In case of unresectable disease, locoregional therapeutic strategies can obtain significant
tumor regression/local disease control rates, but there is no definitive evidence of their effect on patients' survival. In regards to systemic
chemotherapy, the conduction of randomized controlled trials has led to a substantial progress in terms of both
tumor response and survival rates. Despite these results, most patients ultimately die of their disease due to hepatic and/or extra-
hepatic cancer progression. Therefore, novel therapeutic strategies are urgently needed to improve the prognosis of patients with metastatic CRC. The elucidation of CRC biology is paving the way to the development of molecularly targeted strategies, and results from controlled clinical trials have already demonstrated that some agents targeting
tumor-specific molecules can significantly improve the therapeutic efficacy of conventional
antineoplastic drugs. The dissection of the molecular mechanisms of CRC metastatization and
tumor/host interactions will not only accelerate the development of more effective and less toxic anticancer strategies but also will allow for the personalization of the therapeutic regimen according to the molecular features of individual patients and their
tumors. Only the broader clinical implementation of these novel molecular oncology findings and the optimal integration of conventional and molecularly targeted therapeutic approaches will enable clinicians to provide patients with a better chance of cure.