Hepatocellular carcinoma (HCC) is the most common type of liver cancer and one of the leading causes of cancer deaths worldwide.
Some forms of HCC are especially aggressive, making them hard to treat with standard therapies.
One of these particularly dangerous variants grows in thick, layered structures around blood vessels, effectively sealing them in.
This structure—known as the macrotubular/vascular encapsulation (MT/VE) pattern—not only helps the tumor grow but also blocks the immune system from attacking it.
A new study published in Hepatology by researchers at the Institute of Science Tokyo in Japan offers hope for tackling this tough-to-treat cancer.
Led by Professor Shinji Tanaka and Assistant Professor Shu Shimada, the team found that combining two treatment approaches—blocking the tumor’s blood supply and reactivating the immune system—could shrink these tumors and make them more vulnerable to attack.
Using advanced techniques like bulk and single-cell RNA sequencing, the researchers studied over 228,000 individual cells and data from 691 liver cancer samples.
They identified a highly aggressive form of HCC called molecular subtype 1 (MS1). Tumors in this group are made up of fast-dividing cells with high metabolic activity, often fueled by increased glucose processing or fat production.
The MS1 subtype is linked to mutations in the TP53 gene, which normally acts as a cancer-fighting safeguard, and overactivation of MYC, a gene that drives rapid cell growth.
These tumors also have fewer T cells—key immune cells that attack cancer—making it easier for the disease to evade the body’s defenses.
To better understand how to treat this subtype, the team developed a mouse model that closely matched the characteristics of MS1 tumors. The mice were implanted with liver cancer cells that lacked the Trp53 gene and overproduced MYC, resulting in tumors with the same MT/VE structure and aggressive behavior seen in patients.
When the researchers treated these mice with a combination of an angiogenesis inhibitor (to stop the tumor from forming new blood vessels) and an anti-PD-1 antibody (an immune checkpoint inhibitor that “releases the brakes” on T cells), the results were striking.
The tumors shrank significantly, suggesting that the dual approach could break down the tumor’s protective structure and allow the immune system to fight back.
“For MT/VETC-type liver cancer, combining potent anti-angiogenic agents with immune checkpoint inhibitors resulted in significant tumor shrinkage,” Tanaka said. “This strategy could be an effective treatment option for patients with this aggressive form of liver cancer.”
While more research and clinical trials in humans are needed, this study points to a promising new way to treat one of the most challenging forms of liver cancer, potentially improving both survival rates and quality of life for patients.
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Source: KSR.
