Targeted therapy by molecular biomarkers in liver cancer patients

Based on World Health Organization reports, the number of deaths from liver cancer will increase by up to one million by ۲۰۳۰ as a major threat to people. The two common types of liver cancer are hepatocellular carcinoma (HCC) and cholangiocarcinoma, which represent up to ۹۰% and ۶% of all primary liver cancers, respectively. Liver cirrhosis, hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, and alcoholic or nonalcoholic fatty liver disease are known as the main risk factors of susceptibility to liver cancer. Although liver resection, ablation, and liver transplantation are applied as current therapeutic approaches in liver cancer patients, they essentially need to be diagnosed in the early stages. The main challenge in therapeutic approaches to HCC is high heterogeneity that manifests as substantial differences in molecular characteristics between patients. This heterogeneity caused restrictions in the systematic treatment of HCC patients. Targeted therapy has the advantage of precise targeting and low toxicity and can effectively improve HCC treatment. Based on recent evidence, precision medicine, clinical diagnoses, and novel therapeutic approaches have provided breakthroughs in HCC care. In addition, revealing new biomarkers and the trustworthy achievement of liquid biopsy technologies have shown early diagnosis and treatment of HCC. Furthermore, targeted therapy and immunotherapy have given scientists more options for HCC treatment. Recent advanced technologies, including genomics, transcriptomics, and metabolomics, help us better understand the progression and development mechanisms, heterogeneity, and genetic mutation features of HCC. The first approved systemic drug for curing advanced HCC was a vascular endothelial growth factor (VEGF) family multi-kinase inhibitor (anti-angiogenic factor) known as Sorafenib. It can be applied in combined with transarterial chemoembolization (TACE) for advanced HCC. After the sorafenib application, Nivolumab was the first ICI approved as a second-line therapy in advanced HCC. Pembrolizumab is another anti PD ۱ antibody approved by the US FDA. Second line targeted factors for HCC are regorafenib, cabozantinib, and ramucirumab. Regorafenib is a multi-kinase inhibitor that suppresses the VEGFR protein family, PDGFR B, B RAF, c KIT, FLT۳, and RET. Third, Cabozantinib is another multikinase inhibitor that can apply effectively HCC patients with sorafenib tolerance. The other therapeutic strategy for liver cancer patients is tumor immunotherapy, which aims to control tumors following intrinsic immune response, such as cytotoxic T lymphocyte associated antigen ۴ (CTLA ۴), PD ۱ and its ligand PD L۱, which inhibit T cells from recognizing and rescuing cancer cells, and combined immunotherapy. Comprehending the heterogeneity of HCC comprise of difficulties in therapeutic approaches. The development of biomarkers for selecting appropriate drugs benefit HCC patients and provide this opportunity for early diagnosis and precision therapy. We propose the discovery and validation of novel molecular biomarkers for predicting response to therapy and describing suitable candidates for a specific targeted agent, improving response rates, and restricting toxicity in patients should be the focus of future HCC research.

کلیدواژه ها:

Liver cancer ، Hepatocellular carcinoma ، target therapy ، Biomarkers