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Background: Metastatic CRC (mCRC) is a molecular heterogeneous disease. The aim of this review is to give an overview of molecular-driven treatment of mCRC patients. Methods: A review of clinical trials, retrospective studies and case reports was performed regarding molecular biomarkers with therapeutic implications. Results: RAS wild-type status was confirmed as being crucial for anti-epidermal growth factor receptor (EGFR) monoclonal antibodies and for rechallenge strategy. Antiangiogenic therapies improve survival in first- and second-line settings, irrespective of RAS status, while tyrosine kinase inhibitors (TKIs) remain promising in refractory mCRC. Promising results emerged from anti-HER2 drugs trials in HER2-positive mCRC. Target inhibitors were successful for BRAFV600E mutant mCRC patients, while immunotherapy was successful for microsatellite instability-high/defective mismatch repair (MSI-H/dMMR) or DNA polymerase epsilon catalytic subunit (POLE-1) mutant patients. Data are still lacking on NTRK, RET, MGMT, and TGF-β, which require further research. Conclusion: Several molecular biomarkers have been identified for the tailored treatment of mCRC patients and multiple efforts are currently ongoing to increase the therapeutic options. In the era of precision medicine, molecular-biology-driven treatment is the key to impro patient selection and patient outcomes. Further research and large phase III trials are required to ameliorate the therapeutic management of these patients.

BACKGROUND:\ud Direct Antiviral Agents (DAA) demonstrated high efficacy among HCV-infected patients in registered trials. Nevertheless, the impact of these therapies on liver stiffness measurement(LSM) and liver functionality in "real-life" is not well-known. Aim of the present study was to evaluate the SVR impact on LSM and clinical parameters of DAA-therapy on a real-life population of HCV patients with F3/F4 fibrosis.\ud METHODS:\ud 749 HCV genotype 1-4 patients with F3/F4 hepatitis undergoing antiviral therapy, were consecutively enrolled in four centers of Hepatology of Italy. Clinical, biochemical and imaging data were collected at the baseline(T0), at the End of Therapy(EoT) and after 12 weeks(SVR12).\ud RESULTS:\ud Out of 749 patients, 69.7% was F4 and 30.3% was F3. SVR12 was reached in 97,5%. LSM significantly decreased from T0 to EoT(p<0.001) whereas it did not from EoT to SVR12(p:ns). Moreover, in F4 no significant differences were found in Child and MELD between T0, EoT and SVR12(p=ns). At the univariate analysis of clinical and liver parameters, baseline high glucose(p<0.005), type 2 diabetes(p<0.001), low ALT(p<0.001), low PLTs(p<0.005), and the presence of esophageal varices (EV)(p<0.001) were found to be associated with a lack of a significant EoT LSM improvement. At a multiple regression, ALT(p<0.05), Diabetes(p<0.005) and EV(p<0.05), were inversely associated with significant LSM reduction.\ud CONCLUSIONS:\ud Virological response to DAA is associated with fibrosis regression and recovery of liver functionality and this can be detected as early as EoT. HCV eradication is associated with a rapid and significant clinical improvement that lasts overtime and seems to be negatively influenced by diabetes and E

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