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Treatment Strategies for Advanced Liver Cancer

There are several types of liver cancer in adults. The two most common types are hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). HCC is where there are tumours developing within the liver cells and ICC is where the tumours develop in parts of the bile ducts within the liver. There are several risk factors that spur the development and progression of liver cancer. 

The biggest risk factor for HCC is cirrhosis, a disease that occurs when scar tissue forms in the liver and prevents it from working correctly. However, only 3% to 5% of people with cirrhosis will develop HCC. Several studies are being conducted to check if the drugs used to treat other diseases will be able to prevent the progression of cirrhosis to liver cancer. The drugs being tested are statins (for treating cholesterol variations) polyphenols and erlotinib (used to treat non-small cell lung cancer and pancreatic cancer). 

A hepatitis B virus or a hepatitis C virus is also capable of triggering liver cancer. The virus can leave behind parts of its machinery which can activate the oncogenes thus triggering a cancer pathway. People with chronic hepatitis C infections may be treated with antiviral drugs that attack the hepatitis C virus itself and can thus prevent HCC. In a 2019 study funded by the National Cancer Institute, direct acting antivirals were able to improve the symptoms seen in patients who suffered from HCC caused by an HCV infection. 

Inflammation of the colon (colitis) and of the bile ducts (primary sclerosing cholangitis) are risk factors for ICC. In such conditions the gut bacteria can leak into the liver due to an imbalance in the gut microbiome. This leaking can activate certain immune cells (myeloid derived suppressor cells) which suppresses antitumor immunity and in turn promotes liver cancer growth. Many researchers think that this gut bacteria and the associated immune cells could be targets for antitumor medication. A recent study (2021) also found out that neomycin, an antibiotic used to prevent bacterial infections during gastrointestinal surgeries, was able to block the accumulation of myeloid derived suppressor cells and inhibit tumour growth. 

Liver cancer is often diagnosed at an advanced stage. Treatment options for advanced liver cancer include targeted therapy, immunotherapy, radiation, embolization, and ablation.

  • Targeted therapy: 

Targeted therapies are drugs or other substances that specifically attack molecules that aid cancer cells to grow, divide, and spread. Sofrafenib (Nexavar) was the most common targeted therapy option for treating liver cancer for years. Sofrafenib is a kinase inhibitor and it is also used to treat kidney and thyroid carcinomas. Other drugs that have been recently approved for treating HCC include: Ramucirumab, a monoclonal antibody that treats solid tumours and Carboztinib, an oral tyrosine kinase inhibitor.  

  • Immunotherapy

Several immune checkpoint inhibitors are currently approved to treat liver cancer: Nivolumab, a monoclonal antibody that enables programmed cell death to occur by binding to molecules which suppresses the process; Pembrolizumab enhances the cytotoxic activity of T-cells against cancer cells and Atezolizumab is given for liver cancer that has spread or that can’t be treated with surgery. Atezolizumab is the only approved immunotherapy in India for HCC. 

  • Radiation Therapy

Many trials are being done comparing proton therapy to standard photon therapy for people with HCC that cannot be removed by surgery. Proton therapy is a new kind of radiation therapy that may cause less harm to healthy tissues. Other trials are also testing a new type of radiation therapy where the radiation is delivered directly to the tumor, which may cause less harm to healthy tissues. 

  • Transarterial Therapy

People with advanced liver cancer can be treated with therapies that are put directly into the blood vessels that feed their tumors. Transarterial therapy, also called transarterial embolization, involves placing small beads into the blood vessels to cut off blood flow to the tumor. Researchers are exploring ways to enhance transarterial therapy, such as using radioactive beads that not only block blood flow but also deliver radiation to the tumor. 

  • Liver Tumour Ablation Techniques

Ablation therapies kill a liver tumor instead of removing it. In these techniques, doctors use a probe to kill tumors with hot energy. This minimally invasive approach is most effective for smaller tumors less than 3 cm.

Liver cancer when diagnosed at an early stage has a good chance of being cured with surgery alone, surgery and liver transplantation, or nonsurgical treatments such as radiofrequency ablation. Scientists are working to find biomarkers in blood, urine, or other body fluids that might indicate the presence of early-stage liver cancer. Early detection and appropriate treatment can help to improve quality and increase the lifespan for liver cancer patients. 

Author: Parvathi Nair

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