Interdependent and independent multidimensional role of tumor microenvironment on hepatocellular carcinoma

The novelty of an effective therapeutic targeting for hepatocellular carcinoma (HCC) is based on improved understanding of each component of tumor microenvironment (TME) and its correspondent interactions at biological and molecular levels. In this context, new expansions for the treatment against TME and its communication with HCC are under exploration. Despite of the fact that blockage of growth factor receptors has become a treatment of choice in late phases of HCC in clinical practice, still a precise targeted treatment should address all the components of TME. Targeting one specific element out of cellular (cancer associated fibroblasts, endothelial cells, hepatic stellate cells, Kupffer cells and lymphocytes) or non-cellular (extracellular matrix, growth factors, inflammatory cytokines, proteolytic enzymes) parts of TME may not be a successful remedy for the disease because of well-designed hindrances of each component and their functional alternativeness. Meanwhile there are some elements of TME like epithelial-mesenchymal transition and CAF, which are considerably important and need thorough investigations. Ascertaining the potential role of these elements, and a single or combinational drug therapy targeting these elements of TME simultaneously, may provide the appreciable considerations to eventually improve in clinical practices and may also minimize the chances of reoccurrence of HCC.