Recent Progress in Systemic Therapy for Advanced Hepatocellular Carcinoma

Abstract

Patients with advanced hepatocellular carcinoma (HCC) have several systemic treatment options. There are many known risk factors for HCC, and although some, such as hepatitis C, are now treatable, others are not. For example, metabolic dysfunction-related chronic liver disease is increasing in incidence and has no specific treatment. Underlying liver disease, drug resistance, and an increasing number of treatment options without specific biomarkers are all challenges in selecting the best treatment for each patient. Conventional chemotherapy is almost never used for advanced-stage disease, which instead is treated with immunotherapy, tyrosine kinase inhibitors, and VEGF inhibitors. Immune checkpoint inhibitors targeting various receptors have been or are currently undergoing clinical evaluation. Ongoing trials with three-drug regimens may be the future of advanced-stage HCC treatment. Other immune-modulatory approaches of chimeric antigen receptor-modified T cells, bispecific antibodies, cytokine-induced killer cells, natural killer cells, and vaccines are in early-stage clinical trials. Targeted therapies remain limited for HCC but represent an area of potential growth. As we shift away from first-line sorafenib for advanced HCC, clinical trial control arms should comprise a standard treatment other than sorafenib, one that is a better comparator for advancing therapies.

Construction and Validation of a Novel Model for Guiding Targeted Combined Immunotherapy in Advanced Hepatocellular Carcinoma

“…In contrast, our research takes a more comprehensive approach, incorporating multiple predictive factors and applying these models to a larger cohort of patients. This broader perspective allows for a more nuanced understanding of the complex interplay between various biomarkers and their predictive value in the context of HCC immunotherapy [23,24] .…”

Identification and Validation of Basement Membrane Related LncRNA Signatures as a Novel Prognostic Model for Hepatocellular Carcinoma

“…Chemotherapy is a common treatment for advanced HCC but the development of drug resistance presents a significant challenge to treatment and prognosis improvement, making the enhancement of chemosensitivity of great clinical importance (Chouhan et al 2020;Villanueva et al 2019;Bejjani and Finn 2022;Sadagopan and He 2024). Drug sensitivity analysis showed that low-risk patients respond better to cisplatin, gemcitabine, and sorafenib, while high-risk patients are more responsive to 5-fluorouracil, dasatinib, and gefitinib.…”