推进肝细胞癌精准医学：液体活检、免疫微环境、单核苷酸多态性和转化治疗中的当前挑战与未来方向

Hepatocellular carcinoma (HCC) remains a health concern characterized by heterogeneity and high mortality. Surgical resection, radiofrequency ablation, trans-arterial chemoembolization, and liver transplantation offer potentially curative treatments for early-stage disease, but recurrence remains high. Most patients present with advanced-stage HCC, where locoregional therapies are less effective, and systemic treatments-primarily multi-kinase inhibitors and immune checkpoint inhibitors-often yield limited responses. Precision medicine aims to tailor therapy to molecular and genetic profiles, yet its adoption in HCC is hindered by inter-/intra-tumoral heterogeneity and limited biopsy availability. Advances in molecular diagnostics support reintroducing tissue sampling to better characterize genetic, epigenetic, and immunological features. Liquid biopsy offers a minimally invasive method for capturing real-time tumor evolution, overcoming spatial and temporal heterogeneity. Artificial intelligence and machine learning are revolutionizing biomarker discovery, risk stratification, and treatment planning by integrating multi-omics data.

Immunological factors such as tumor-infiltrating lymphocytes, natural killer cells, macrophages, and fibroblasts have emerged as determinants of HCC progression and treatment response. Conversion therapy-combining systemic agents with locoregional treatments-has showndemonstrated promise in downstaging unresectable HCC. Ongoing efforts to refine biomarker-driven approaches and optimize multi-modality regimens underscore precision medicine's potential to improve outcomes. PubMed (January 2002-February 2025) was searched for relevant studies.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer and continues to be a major health problem worldwide. While early-stage HCC can sometimes be cured with surgery or liver transplantation, most patients are diagnosed when the cancer is advanced. Current treatments for advanced disease often do not work well for many patients. Precision medicine, a new approach that tailors treatments to each patient’s unique genetic makeup and tumor biology, shows promise for improving outcomes in HCC.

However, the complex nature of this cancer makes finding effective personalized treatments challenging. Liquid biopsies—a simple blood test to detect cancer cells or genetic material from the tumor—are becoming an important tool. TheyLiquid biopsy can capture thegenetic changes in a tumor over time without the need for repeated invasive biopsies.

The immune system’s interaction with cancer is another critical factor in determining how well patients respond to treatments. Recent research has identified that genetic differences between individuals can significantly impact their immune response to tumors.

Additionally, new strategies known as conversion therapies—combining medication and targeted local treatments—are helping some patients with advanced HCC undergo surgery that was previously not possible. Advances in artificial intelligence (AI) are also improving the identification of important biomarkers and helping doctors select the best treatments for each patient.

Overall, continued development in these areas offers hope for more effective and personalized care for patients with liver cancer.