# Hepatocellular Carcinoma: Current Drug Therapeutic Status, Advances and Challenges

## TL;DR

Hepatocellular carcinoma remains a deadly cancer with limited treatment options, but new therapies like immunotherapy offer hope despite challenges like drug resistance and lack of biomarkers.

## Contribution

The paper reviews current drug therapies, recent advances, and ongoing challenges in treating hepatocellular carcinoma.

## Key findings

- Molecular targeted therapy and immunotherapy have transformed systemic treatment for hepatocellular carcinoma.
- Drug resistance, tumor heterogeneity, and lack of effective biomarkers remain major challenges in treatment.
- Most patients are diagnosed at intermediate or advanced stages, limiting curative treatment options.

## Abstract

Hepatocellular carcinoma is the second leading cause of cancer-related deaths and the seventh most common cancer worldwide. Although there have been rapid developments in the treatment of hepatocellular carcinoma over the past decade, the incidence and mortality rates of hepatocellular carcinoma remain challenging. Only about 30% of patients can be treated with curative methods, while over 50% of patients require systemic treatment to prolong survival, with a limited benefit. Molecular targeted therapy and immunotherapy have brought about a revolution in hepatocellular carcinoma systemic treatment. Nevertheless, the treatment of hepatocellular carcinoma is still a challenge due to significant drug resistance, tumor heterogeneity, lack of druggable mutation targets, and lack of effective biomarkers. To improve outcomes of hepatocellular carcinoma patients, we need to gain a deeper understanding of the hepatocellular carcinoma genome and explore more combination treatment regimens.

Hepatocellular carcinoma (HCC) is the most common form of liver cancer, accounting for ~90% of liver neoplasms. It is the second leading cause of cancer-related deaths and the seventh most common cancer worldwide. Although there have been rapid developments in the treatment of HCC over the past decade, the incidence and mortality rates of HCC remain a challenge. With the widespread use of the hepatitis B vaccine and antiviral therapy, the etiology of HCC is shifting more toward metabolic-associated steatohepatitis (MASH). Early-stage HCC can be treated with potentially curative strategies such as surgical resection, liver transplantation, and radiofrequency ablation, improving long-term survival. However, most HCC patients, when diagnosed, are already in the intermediate or advanced stages. Molecular targeted therapy, followed by immune checkpoint inhibitor immunotherapy, has been a revolution in HCC systemic treatment. Systemic treatment of HCC especially for patients with compromised liver function is still a challenge due to a significant resistance to immune checkpoint blockade, tumor heterogeneity, lack of oncogenic addiction, and lack of effective predictive and therapeutic biomarkers.