**6. Future perspective**

Although, various drugs have been tested and approved for advanced HCC, but one of the main reasons of low survival rate is drug resistance because of the intratumor heterogeneity during treatment. This is a huge hurdle for the long-term use of targeted therapies for primary liver cancer, that is why it is essential to explore the mechanism of drug resistance in future. Another challenge for targeted treatments is the deficiency of accurate targets and biomarkers such as breast cancer has the exact biomarker like HER2, but primary liver cancer has no accurate biomarkers and show heterogeneity and genomic diversity. While many mutant genes such as TERT and CTNNB1, have been found, but it is still not clear as they are driver gene or passenger gene in future, it is essential to understand the genomic architecture, mutation landscape, and driver genes to use new therapeutic interventions. Most of the patients are not adaptable to immune therapy, therefore future efforts in should be made in two directions for immunotherapy such as improving the existing immune response and stimulating a new immune response. Moreover, further study is undoubtedly compulsory to advance improvement in current diagnosis, to better comprehend the genomic profile and pathogenesis of HCC to develop novel therapeutics, containing multiple drugs or treatments, that capable of modifying various signaling and biological pathways associated with HCC pathogenesis.

*Liver Cancer - Genesis, Progression and Metastasis*
