**6. Conclusions and future perspectives**

As we have already seen, there are several types of thermal-based therapies that have shown modest efficacy in HCC treatment. Unfortunately, simple heating techniques have trouble discriminating between tumors and surrounding healthy tissues. Moreover, the use of thermal therapies in large HCC is of limited value. In order to overcome these limitations many groups have investigated the use of NPs to increase the tumor ablation zone.

There are many types of NPs, each type with its own major advantages and disadvantages. Based on currently available literature, we could not say which of the above-described NPs is better for the long-term management of HCC. Unfortunately, there are no studies comparing AuNPs with carbon nanoparticles or magnetic nanoparticle. The use of NPs such as AuNPs, carbon nanoparticles, and magnetic nanoparticles have shown great promise as light absorbers for cancer therapy, demonstrating an ability to destroy cancerous lesions both in vivo and in vitro [31].

We believe that an ideal NP should be a good light absorber in order to achieve complete ablation of the tumor tissues. To avoid systemic toxicity, the NPs should show selective accumulation in target tissue with minimal nonspecific distribution. Not at least, they should be rapidly cleared from the body after their mission to prevent redistribution into off-target sites [38].

Future research should focus on the development of multifunctional NP. For instance, theranostic agents could improve both the diagnostic accuracy and therapy of HCC. Small HCC means better outcomes. The majority of NPs are functionalized to target the tumor cells, leaving the tumor stroma unaffected. A pro-tumorigenic stroma or better said a pro-tumori‐ genic microenvironment could lead to tumor recurrence, therefore dual targeting of both tumor cells and tumor stroma could overcome these limitations.

Specific targeting in HCC is still a major problem. There are many molecular pathways involved in HCC development. Moreover, not all HCC express the same receptors on the cell surface. In order to specifically deliver NP in the tumor area, immunohistological staining must be performed. This is hard to perform, particularly in HCC, since liver biopsy is no longer recommended for HCC diagnosis. Maybe it is time to go back where we started and reconsider the role of liver biopsy in HCC management.

In the last 50 years, despite tremendous advances in our knowledge of the molecular mecha‐ nism of cancer, there has been no change in the age-adjusted mortality from cancer [39]. This data clearly suggests that what we are doing now is wrong and an individualized treatment could bring new hopes for HCC patients.
