Hepatocellular carcinoma (HCC) is the fifth most frequent cancer form but the second leading cause of all cancer-related deaths. There are several reasons for high mortality in the HCC cohort: lack of effective screening programs and consequently late diagnosis, multifactorial origin with cumulative risk factors, complex carcinogenesis, tumor heterogeneity, unpredictable impacts of individual microenvironment on tumor development and progression, and, as the consequence, frequently untargeted therapy and cancer resistance toward currently applied treatment approaches. The currently applied ‘treat and wait’ approach is inappropriate in the overall HCC management. Urgent need in paradigm change toward predictive, preventive and personalized medicine is discussed in this review article. Innovative strategies for an advanced predictive, preventive and personalized medicine approach in the overall HCC management benefiting the patient are presented.
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