Nature Series Review: The team of Qin Wenxin/Wang Cun of Shanghai Jiaotong University summarizes the therapeutic prospects of advanced liver cancer

Liver cancer is a malignant tumor
with multi-gene participation, multifactorial mediation and complex pathological mechanism.
According to the latest statistics from the International Agency for Research on Cancer (IARC/WHO) under the World Health Organization, there were about 906,000 new cases of liver cancer and 830,000 deaths worldwide in 2020, of which about 50% of cases occurred in China
.

Liver cancer mainly includes hepatocellular carcinoma, intrahepatic cholangiocarcinoma and hepatoblastoma, hepatocellular carcinoma (HCC) is the main type of primary liver cancer, accounting for about 85%-90%
of liver cancer patients.
For patients with early-stage liver cancer, surgical resection and liver transplantation are effective treatments
.
Due to the difficulty of early diagnosis of liver cancer and the rapid progression of the disease, most patients have progressed to the middle and advanced stages when they are diagnosed, and the opportunity
for surgery has been lost.
For these patients, systemic therapy improves overall survival
.

Recently, Qin Wenxin and Wang Cun's team from the Shanghai Cancer Institute of Renji Hospital affiliated to Shanghai Jiao Tong University School of Medicine published a long review entitled Gastroenterology & Hepatology, a review
journal under Nature.

This review comprehensively summarizes the latest progress in clinical treatment and preclinical research of advanced liver cancer, and puts forward insights and thoughts
on the bottleneck and future development trend of liver cancer research.

Current FDA (US Food and Drug Administration) approved first-line therapies for advanced liver cancer include Sorafenib, Lenvatinib and Atezolizumab (PD-L1 inhibitor) in combination
with Bevacizumab (angiogenesis inhibitor).

It is worth mentioning that compared with Sorafenib monotherapy, the combination therapy of Atezolizumab and Bevacizumab can significantly prolong the survival of liver cancer patients, and the overall response rate of patients can reach 27.
3%, and the median overall survival can reach nearly 20 months
.
In addition to FDA-approved therapies, many new liver cancer therapies are in clinical trials in recent years
.
These new therapies can be divided into the following three categories: targeted drug therapy, immunotherapy, combination therapy strategies, etc
.

The team of Qin Wenxin and Wang Cun elaborated on the combination therapy strategy of advanced liver cancer, and divided it into the following five categories: combination therapy based on targeted drugs, combination therapy based on immune drugs, combination of immune drugs and angiogenesis inhibitors, combination of immune drugs and multi-target kinase inhibitors, and combination of immune drugs and other drugs.

Combination therapy strategies for liver cancer

The review further analyzes the possible challenges and potential opportunities
for systemic treatment of advanced HCC.
At present, systemic treatment of liver cancer lacks effective biomarkers
.
Qin Wenxin and Wang Cun's team summarized potential candidate markers for targeted therapy and immunotherapy, and discussed potential intervention strategies
for high-frequency mutations in liver cancer (such as TERT promoter, TP53, CTNNB1, etc.
).
The article also introduces the treatment concepts that are still in the conceptual stage of liver cancer treatment, such as One-two punch (step-by-step treatment strategy), Syntheticlethality, etc.
, these new treatment concepts will help deepen the understanding of liver cancer treatment and open up new potential treatment strategies
.

This is the second long review in the Nature series published by the team in the field of liver cancer research in the past two years
.
In 2021, Qin Wenxin's team published a long review in Nature Reviews Gastroenterology & Hepatology with the title: Exploring liver cancer biology through functional genetic screens, summarizing the application of
functional gene screening technology in liver cancer research.

Professor Qin Wenxin and Wang Cun of Shanghai Cancer Institute, Professor René Bernards of the Netherlands Cancer Institute, Professor Andrew X.
Zhu of the Cancer Research Center of Massachusetts General Hospital and Shanghai Jiahui International Cancer Center are the corresponding authors of the latest review paper, and Dr.
Chen Yang and Dr.
Hailin Zhang of Shanghai Cancer Institute are the first authors
.