Precision Medicine for Hepatocellular Carcinoma: Clinical Perspective

Abstract

Hepatocellular carcinoma (HCC) is one of the major malignant diseases worldwide, characterized by growing incidence and high mortality rates despite apparent improvements in surveillance programs, diagnostic and treatment procedures, molecular therapies, and numerous research initiatives. Most HCCs occur in patients with liver cirrhosis, and the competing mortality risks from the tumor and the cirrhosis should be considered. Presently, previously identified risk factors, such as hepatitis virus infection, hepatic inflammation and fibrosis, and metabolic syndrome, may be used as chemoprevention targets. The application of precision medicine for HCC management challenges the one-size-fits-all concept; moreover, patients should no longer be treated entirely according to the histology of their tumor but based on molecular targets specific to their tumor biology. Next-generation sequencing emphasizes HCC molecular heterogeneity and aids our comprehension of possible vulnerabilities that can be exploited. Moreover, genetic sequencing as part of a precision medicine concept may work as a promising tool for postoperative cancer monitoring. The use of genetic and epigenetic markers to identify therapeutic vulnerability could change the diagnosis and treatment of HCC, which so far was based on Barcelona clinic liver cancer (BCLC) staging. In daily clinical practice, the shift from a stage-oriented to a therapeutic-oriented approach is needed to direct the choice of HCC treatment toward the potentially most effective option on an individual basis. The important factor in precision medicine is the promotion of patient management based on the individual approach, knowing that the final decision must be approved by a multidisciplinary expert team.

KLF4 loss in hepatocellular carcinoma: Improving prognostic prediction and correlating immune infiltrates

“…In the latest clinical trials RATIONAL 301 study (tislelizumab versus sorafenib for HCC), tislelizumab monotherapy demonstrated positive results with a 14.3% overall response rate (Qin et al, 2022). Yet the precise biomarkers for predicting tumor immunotherapy efficiency are still lacking and the development of prognostic markers is necessary (Galun et al, 2022). Recent research indicates that T cells in a state of exhaustion can serve as medication guidance for tumor immunotherapy (Binnewies et al, 2018).…”

Development of a hepatocellular carcinoma imaging database and structured imaging reports based on PACS, HIS, and repository

“…The proposed platform takes computed tomography/magnetic resonance imaging (CT/MRI) of liver as the core and incorporates clinically relevant data, including patients’ basic data, examination-related data, and diagnostic and therapeutic data, providing a comprehensive database for the accurate diagnosis and structured imaging reports of HCC. The structured imaging report should include the following contents: quantitative analysis of tumor, liver imaging reporting and data system (LI-RADS) ( 11 ), HCC staging ( 12 ), treatment method ( 13 – 16 ), and other significant information. The DICOM C-MOVE command was utilized in the PACS system, which automatically collects, archives, permanently online stores the original images and diagnostic reports of pathologically confirmed HCC cases in real-time, and automatically retrieves clinically relevant data and sync matching and archiving.…”

Metabolomics in hepatocellular carcinoma: From biomarker discovery to precision medicine

“…Therefore, the integrated analysis of multi-omics data can provide comprehensive information from different molecular insights. In this regard, multi-omics analysis in an integrated framework has been proposed with great potential to facilitate biomarker discovery and treatment guidance in future clinical therapy ( 6 , 26 , 27 ).…”