Liver cancer research

All new treatments have to be fully researched before they can be adopted as standard treatment for everyone. This is so

• We know they are safe
• We can be sure they work
• We know they work better than the currently available treatments

Possible new treatments are developed and tested in laboratories. For ethical and safety reasons, experimental treatments must be tested in the laboratory before they can be tried in patients. If a treatment described here is said to be at the laboratory stage of research, it is not ready for patients and is not available either within or outside the NHS.

All the new approaches covered here are the subject of ongoing research. Until studies are completed and new effective treatments are found, these treatments cannot be used as standard therapies for cancer of the liver. We just don't know if they work. Or work better than what is available at the moment.

If you are interested in taking part in a clinical trial, you should ask your specialist if there are any current studies that you may be suitable for. Unfortunately, there are not that many trials for primary liver cancer treatment in the UK as it is not a common cancer in this country. It can take such a long time to recruit enough people for studies into rare cancers that the trials become very difficult to do at all. Much of the research into liver cancer takes place in countries where it is more common.

New treatments for liver cancer are always tested first in clinical trials. This is fully explained in the clinical trials section. Early research is usually restricted to people for whom all other possible treatments have been tried.

If you are interested in taking part in a clinical trial, visit our searchable database of clinical trials in the UK. Choose 'liver' from the dropdown menu. The database also has information about closed trials and trial results.

If there is a trial you are interested in, print it off and take it to your specialist. If the trial is suitable for you, your doctor will need to make the referral to the research team. 

Research is going on all around the world looking at ways to prevent liver cancer developing. The main areas of interest include

• How liver cancer cells work and the genetics of liver cancer
• Risk factors of liver cancer such as hepatitis B and C, drinking alcohol, and exposure to aflatoxins
• Controlling hepatitis to try to control liver cancer

We hope that within the next 10 years this research will tell us much more about why liver cancer develops, and ways to reduce the rate across the world.

About 400 million people worldwide are carriers of the hepatitis B virus. It is likely that between 2 and 5 out of every 10 of these people (about 25 to 50%) will eventually die of liver cirrhosis or hepatoma (HCC). But the rest of those infected will never develop a fatal liver disease. The big question for researchers is why some people carrying the hepatitis virus get hepatomas and others don't. The environment and genetics may play a role in this.

Hepatitis infection is the major cause of hepatoma, and some scientists believe that vaccinations and better ways of treating hepatitis could halve the number of hepatoma cases worldwide. Hepatitis B vaccines have been available since the 1980's, and there have been mass vaccination programs in Asia, Africa and parts of Europe. We should have some more definite answers on how well mass vaccination is working in the next 20 years or so.

Unfortunately, there is not yet a vaccine against hepatitis C. This virus is widespread in some countries. Hepatitis C is also linked to cirrhosis and liver cancer. So as the incidence of hepatitis increases, so will the incidence of liver cancer unless a vaccine can be found and mass vaccination arranged in the most affected countries.

There are medicines that can control hepatitis C infection, including interferon and ribavirin. But they do not work for everybody. And if there has already been damage to the liver, even if the virus is well controlled by these medicines, there is still a risk of developing hepatoma many years later. 

There has been some research looking into interferon as a way of stopping liver cancer developing in people who have hepatitis C infection. The studies show that giving interferon lowered the rate of primary liver cancer, but about 1 in 3 patients still developed hepatoma compared with just under 1 in 2 without giving interferon. Interferon seemed to help more if the hepatitis C had already been cured. More research needs to be done in this area.

In Cambridge, a small study is looking at MRI scans to find out more about cancer of the liver. The researchers want to find out if newer types of MRI scans can help to diagnose liver cancer, and also whether extra MRI scans during treatment can help doctors to work out the best type of treatment.

Clinical trials are continuing to examine the use of chemotherapy drugs for treating liver cancer. There is research testing completely new drugs, and drugs that have been used successfully for other types of cancer.

Doctors are also continuing to study chemoembolisation treatment. This is a way of delivering the chemotherapy directly to the area of the liver that contains the cancer. Doxorubicin is the drug doctors use most when giving chemotherapy this way. You have the chemotherapy with something to block the blood flow to the tumour. This might be tiny plastic beads or a type of gel. Blocking the flow of blood helps to kill the cancer cells by keeping the chemotherapy in the liver for longer. It also cuts off the tumour's food and oxygen supply.

A Cochrane review in 2011 looking at all of the research into chemoembolisation and embolisation for liver cancer found that there is not enough evidence to recommend it as a standard treatment at the moment. They say we need more research.

One trial is comparing chemoembolisation to embolisation (where the blood supply to the tumour is cut off without chemotherapy). This is called the TACE trial. The trial is now closed and we are waiting for the results. The TACE 2 trial is combining a biological therapy drug called sorafenib with chemoembolisation.

Biological therapies are treatments with substances derived from the human body. There are many different types of biological therapies. One type is called growth factor blockers. They are designed to stop cancer cells growing. Tyrosine kinase inhibitors (TKI for short) are a type of growth factor blocker. Tyrosine kinase is a chemical messenger (enzyme) that plays a part in the growth of cancer cells.

One TKI is called sorafenib. It blocks a number of enzymes, so it is known as a multiple kinase inhibitor. It comes as a tablet. In October 2007 sorafenib was approved in Europe as a treatment for hepatocellular carcinoma (HCC), the most common form of primary liver cancer. The SHARP (Sorafenib Hepatocellular Carcinoma Assessment Randomized Protocol) trial found that sorafenib when compared with a placebo can help people with advanced liver cancer to live a couple of months longer. The trial was for people who had not had any other treatment and were unable to have surgery. 

In May 2010 the National Institute for Health and Clinical Excellence (NICE) issued final guidance that sorafenib is not approved as an NHS treatment for people with advanced hepatocellular cancer. This includes people whose treatment is no longer working and those who cannot have surgery or other local treatments. NICE and the Scottish Medical Council (SMC) do not recommend sorafenib because they say it is not cost effective. There is more information about how NICE makes decisions in our question and answers section.

You may be able to have sorafenib as part of a clinical trial. Some studies are underway testing sorafenib combined with chemotherapy or with chemoembolisation. If you would like to read more about these trials, visit our clinical trials database. Select 'liver' from the dropdown menus of cancer types.

There is research combining the drug thalidomide with chemotherapy. Thalidomide is type of drug called an anti angiogenic. This means that may be able to stop a cancer from growing its own blood supply. Without its own blood vessels, a cancer cannot grow much larger than a pea. Thalidomide has been tested on various cancer types. The results generally haven't been as successful as first hoped. So now, researchers are trying thalidomide in combination with chemotherapy.

A trial for children and young adults (up to the age of 29) with HCC has been looking at whether thalidomide can make treatment with chemotherapy, and surgery or chemoembolisation, more effective. This trial is called SIOPEL 5. This trial is no longer recruiting patients, and we are waiting for the results.

A trial is looking at a new drug called ADI-PEG 20 for advanced liver cancer. Liver cancer cells need an amino acid called arginine to survive and grow. ADI-PEG 20 breaks down arginine and so may stop liver cancer cells growing. This trial will compare ADI-PEG 20 and best supportive care with a dummy drug (placebo) and best supportive care.

Another trial is looking at a new drug called GC33 for liver cancer that has spread. GC33 is a type of monoclonal antibody. They can seek out cancer cells by looking for particular proteins on the cells' surface. Some liver cancer cells have a protein called GPC-3 on the surface (GPC-3 positive). Researchers want to find out how well GC33 works for GPC-3 positive hepatocellular cancer (HCC) and what the side effects are.

Pravastatin is one of a group of drugs called statins. These drugs are usually given to people to reduce cholesterol. But doctors think that pravastatin may help chemotherapy to work against some cancers. A small German trial found that patients with advanced liver cancer who had chemoembolisation with pravastatin lived significantly longer than patients who just had chemoembolisation. But more research is needed into using pravastatin this way.

This treatment is similar to radiofrequency ablation (RFA) but uses lasers instead of radio waves to destroy the tumours. A laser is a high energy beam of light that can be used instead of a surgical knife to cut very precisely. An advantage of laser surgery is that it is good at controlling bleeding. This is particularly useful for liver surgery as the liver has a very rich blood supply.

Like radiofrequency ablation (RFA), this treatment uses high energy radio waves. But this time the RFA treatment is combined with surgery. The surgeon uses an ultrasound scan to guide the probe into the right place. Then the radio waves coming from the probe destroy the liver tissue around the cancer. Then the dead tissue is surgically removed (resected) with the tumour.

The idea is that heating up the tissues with the RFA probe will seal blood vessels so that there isn't as much bleeding as there would be with a standard operation to remove liver cancer. In February 2007 the National Institute for Health and Clinical Excellence (NICE) issued guidance saying that this procedure appears to be safe and works well enough to be used on tumours in the liver. But there is a higher risk of getting an infection afterwards, and NICE says there isn't enough evidence yet to show that it is any better than other ways of removing liver cancer during an operation.

A new type of surgery has been developed for people who have liver tumours in parts of the liver that are dangerous or usually impossible to treat with surgery. For example, when the tumour is very close to major veins that connect to the liver. This type of surgery is very new and experimental, and is used when the patient would die if they did not have the surgery. But there is a risk of dying from the surgical operation. The operation involves removing the liver from the body, cutting away the diseased tissue, and then putting back the healthy liver tissue. It is called 'ex-vivo hepatic resection and reimplantation for liver cancer'.

The National Institute for Health and Clinical Excellence (NICE) has issued guidance about this surgery. They say that there is limited evidence for the safety of this type of operation and it is not clear how well it works, but it may be helpful for some people with liver cancer. 

High intensity focused ultrasound (HIFU) is a treatment for different types of cancer, including primary liver cancer. The treatment is given using a machine that gives off high frequency sound waves. These waves deliver a strong beam to a specific part of a cancer. Some cells die when this high intensity ultrasound beam is focused directly onto them.

One advantage of this treatment is that because it only uses sound waves to kill the cancer cells, it doesn’t have as many side effects as other types of cancer treatments already in use.

There is detailed information about HIFU in the question and answer section of CancerHelp UK.

This treatment is similar to radiofrequency ablation, but it uses slightly different energy waves - microwaves - to destroy the liver cancer. The microwaves heat and kill the cancer cells. You can have this treatment for more than one liver cancer tumour. The doctor puts a thin needle into each tumour. The microwaves are released through the needles. For larger tumours, you may have a number of needles put in all attached to the microwave generator, so that the doctor can be sure of getting rid of all the cancer. For microwave ablation you would need a general or a local anaesthetic.

In March 2007 the National Institute for Health and Clinical Excellence (NICE) said that microwave ablation of primary liver cancer (HCC) works well enough to be considered a treatment option.

This type of treatment hasn't been around long enough for us to have a completely clear picture of how much it helps. There needs to be more research into this procedure.

RFA is a treatment used for tumours smaller than 3cm. Researchers in America are looking into combining radiofrequency ablation (RFA) with a new type of liposomal doxorubicin chemotherapy called Thermodox. As with normal liposomal doxorubicin the doctor gives the chemotherapy into the blood stream but it only starts to work when the temperature is above 39.5°C. The treatment aims to reach more of the tumour than the RFA can when you have that on its own. The researchers hope that combining the two treatments it will mean that larger tumours can be treated with RFA. The European Medicines Evaluation Agency (EMEA) has now given it orphan drug status. It will be some time before we know whether this treatment works better than RFA on its own. 

This is similar to chemoembolisation, but instead of chemotherapy it uses radiation. Millions of tiny beads (sometimes called microspheres) are fed into the hepatic artery, the main blood vessel which supplies the liver. These beads block the supply of blood to the cancer. They contain a radioactive substance called yttrrium-90, so they also work by sending out radiation. This helps to kill off the cancer cells. 

This treatment is approved for use in the USA, and it is just beginning to be used in a small number of hospitals in the UK. It is most often used to help with symptoms of liver cancer, rather than to cure it. It can also be used to treat cancer that has spread to the liver (liver metastases).

Primary liver cancer is one of the rarest types of cancer in children. Large hospitals see only a few cases each year and this makes it very difficult to carry out meaningful research to improve treatment. Generally, children with liver cancer have a much better outlook than adults with primary liver cancer. But there are still improvements to be made.

Often, young patients in many hospitals and countries are involved in clinical trials for liver cancer. In this way, enough information can be gathered to find out which treatment is the best, and when it is appropriate to use less intensive treatment so that side effects can be minimised.

Trials for children with primary liver cancer are listed on our clinical trials database. Choose 'children's' and then 'other' from the dropdown list of cancer types. One trial is looking into chemotherapy for a form of childhood liver cancer called hepatoblastoma that has come back after treatment. Hepatoblastoma is often treated with cisplatin chemotherapy, but this can damage hearing. Another trial is looking at giving children treated with cisplatin a drug called sodium thiosulphate, to see if this reduces the risk of hearing loss.

The Children's Cancer and Leukaemia Group (CCLG) has information to support parents and relatives of children having cancer treatment.