Melanoma research

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

• We can be sure they work
• We can be sure they work better than the treatments that are available at the moment
• They are known to be safe

First, 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 as a treatment either in the NHS or in private health care.

Tests in patients are called clinical trials. The trials and research section has information about  what trials are including information about the 4 phases of clinical trials. If you are interested in taking part in a clinical trial, visit our searchable database of clinical trials. Then select 'melanoma' from the drop down menu and click 'find'. If there is a trial you are interested in, print it off and take it to your own specialist. If the trial is suitable for you, your doctor will need to make the referral to the research team.

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 therapy for melanoma.

Most melanomas are preventable. If we can find a way to successfully educate people to protect their skin properly when they go out in the sun we could prevent the majority of skin cancers. Research into this area includes

• National skin cancer prevention campaigns
• Training people to recognise melanoma skin cancer
• Melanotan and sun protection
• Using scanners to detect melanoma
• Genetics
• IMP-3 protein
• Preventing melanoma coming back after treatment

National skin cancer prevention campaigns

Late in 2002, the UK Department of Health commissioned Cancer Research UK to run a national skin cancer prevention awareness campaign. The campaign called SunSmart was launched in March 2003. This pilot paved the way for a continuous campaign for a further 3 to 5 years. We hope this will provide a platform upon which to base a long term sun awareness campaign allowing us to measure its benefits.

Look in the about melanoma section of CancerHelp UK for lots of information about how to protect your skin from the sun. You can also get information on Cancer Research UK's SunSmart website. 

Training people to recognise melanoma skin cancer

There is a UK study looking at the skills people need to help them recognise melanoma skin cancer and to see if these skills could be improved. The trial aims to see if people can match up their skin change with a computer picture to help them decide if it could be melanoma. The researchers hope that this will help people to go to their doctor sooner.  

Melanotan and sun protection

An Australian company has been developing a new drug called afamelanotide, or Melanotan. They hope it will protect people from sunburn. The company are developing it as injections, or as a pellet that releases a drug into your system over about 30 days. The company say one dose could give you an all over tan lasting for months. The pellet is implanted just under your skin and is made of the same material used in dissolvable stitches. Most people don't have any side effects from this material.

This drug is still in early stages of development and we won't know how successful it really is in preventing sunburn for some time. Equally, we can't know how safe it is until it has been in use for some time. Early trials have shown no immediate side effects. But it hasn't been around long enough for us to know if it does any lasting harm. The makers claim this drug will not replace the 'staying safe in the sun' message, but will add to it.

The Medicines and Healthcare Products Regulation Agency (MHRA) is the government agency which makes sure that drugs work well and are reasonably safe. They have advised people in the UK not to use Melanotan because it is unlicensed and we do not know enough yet about how safe it is. They issued this advice in November 2008, because Melanotan has been advertised in some gyms and tanning salons. It is illegal to supply or advertise Melanotan in the UK.

There is more information about Melanotan in the CancerHelp UK skin cancer questions and answers section.

Using scanners to detect melanoma

The MoleMate trial is checking whether a new type of hand held scanner can help GPs to tell the difference between normal moles and melanomas. The scanner is linked to a computer and takes pictures of the moles. The computer analyses the moles and gives a report on whether the mole could be a melanoma. If the scanner works well it will reduce the number of people who are unnecessarily referred to a specialist to have normal moles removed. This trial is now closed and we are waiting for the results. 

A study is looking at a new system called a ‘Skin Analyser’ that takes detailed pictures and shows the texture of abnormal areas of skin. Researchers are using the Skin Analyser to look at areas of abnormal skin, such as moles or skin blemishes, in people with and without suspected skin cancer. They will then look at this information along with results from SIAscopy (hand held scanner test) and physical examination. They hope to use this information to develop a system that can spot suspected skin cancer as accurately as possible.

Genetics

Scientists now know that the ultraviolet light from the sun damages your DNA. These changes in your DNA can  increase the chance of normal skin cells to become cancerous. Scientists are using this information to develop new treatments for skin cancers.

A few people are more at risk of developing melanoma than other people, because they have inherited a high risk faulty gene from a relative. Scientists recently discovered one of these genes, called the p16 gene or CDKN2A. They have been running a long term study to find out more about how genes and your surroundings can affect your risk of developing melanoma. This trial is no longer recruiting patients, and we are waiting for the results.

It is not recommended that everyone has a test for gene faults. This is because the gene is rare and the advice offered to families with melanoma about prevention and regular screening for early signs is the same whether you have the gene or not.

IMP-3 protein

Studies are looking at using IMP-3 protein to detect melanoma. Scientists have found that melanoma cells produce a lot of this protein, while cells from ordinary moles do not. They hope that this will help them diagnose melanoma quicker in the future. This is still very early research.

Preventing melanoma coming back after treatment

A study is looking into how people live, what they eat, and how much time they spend in the sun after they have been treated, to see if any of these factors might increase the risk of the melanoma coming back. This study will also look at the genes of people with melanoma, to find out if any of these affect the risk of recurrence. While this trial is open you can find more details on our clinical trials database. Pick 'melanoma' from the drop down list of cancer types.

When removing melanoma with surgery doctors often remove the nearest lymph node (sentinel node) to see if the melanoma has spread there. This surgery is called sentinel node biopsy. One trial is looking at treatment after sentinel lymph node biopsy for melanoma. At the moment if tests show melanoma cells in the sentinel node the standard treatment is an operation to remove all the other lymph nodes in the area. This is because they may contain cancer cells too.

But lymph node dissection has side effects and doctors are not sure whether it is necessary to remove all the lymph nodes straight away. So in this trial some people will have their lymph nodes removed and some will have monitoring with regular ultrasound scans. The trial aims to find out whether people need to have all their lymph nodes removed. The SUNMEL trial is checking whether ultrasound can find melanoma that has come back in the lymph nodes before it can be felt by hand.

Biological therapy is treatment with substances that are made naturally within the body. The types of biological therapies being researched for melanoma include

• Interferon
• Monoclonal antibodies
• BRAF inhibitors
• MEK inhibitors 
• Drugs that block cell growth
• Vaccines
• Gene therapy
• Tumour necrosis factor (TNF)

You can find out about biological therapy trials for melanoma on CancerHelp UK's clinical trials database.

Interferon

For people with stage 2 or 3 melanoma, there is a risk that the melanoma will come back at some time after their surgery. Doctors are trying to find out whether interferon treatment may help to prevent this. Interferon is made naturally as part of the body's immune response. But it can be made in the laboratory and used in much larger amounts as treatment for cancer and other diseases.

Interferon has also been tried for melanomas that have spread to other parts of the body. It hasn't been shown to be of much benefit so far.

Monoclonal antibodies

Antibodies are proteins made by the cells of the immune system to destroy infection or abnormal cells such as cancer. The antibodies attach themselves to the infectious or cancerous cells and kill them. Our bodies make many different antibodies as part of our immune system's reaction to infection or damaged cells. Each antibody recognises one particular protein on the surface of a foreign or invading cell. A monoclonal antibody (MAB) is a copy of a single antibody made in the lab that can then be made in bulk. Some monoclonal antibodies activate the immune system to seek out and destroy melanoma cells in the body,

One monoclonal antibody is bevacizumab. This is licensed as a treatment for advanced bowel cancer, and has also been used for other cancers. Doctors want to find out if giving it to people with high risk melanoma helps to stop the cancer coming back, after it has been removed surgically. The AVAST-M trial is looking into this. You could join this trial if you have had stage 2B, 2C or 3 melanoma, which has been surgically removed. The aims of this trial are to find out if bevacizumab after surgery can help to stop or delay melanoma coming back. And to find out if there are ways to find out who will benefit most from bevacizumab. 

Trials have found that a monoclonal antibody called ipilimumab can help some people with advanced melanoma to live longer. It is approved in the UK for the treatment of advanced melanoma in people who have already had other treatments. Trials are now looking at other ways of using ipilimumab for melanoma. There is a trial looking at whether ipilimumab can help to stop stage 3 melanoma coming back, after the melanoma has been completely removed by surgery. Doctors running this trial also want to find out more about the side effects of ipilimumab. Another trial is looking at combining ipilimumab with the chemotherapy drug dacarbazine in people with advanced melanoma to see if it helps the chemotherapy work better.

Another monoclonal antibody called CNTO 95 or intetumumab has been tried to see how well it works against advanced melanoma. A small international trial using intetumumab for advanced melanoma combined it with the chemotherapy drug dacarbazine (DTIC). The researchers found that it was safe to use and that it worked very slightly better for some people than dacarbazine on its own. They recommend further research to find out more about intetumumab.

BRAF inhibitors

Research has shown that a protein called BRAF is faulty in about half the people who have melanoma skin cancer. The BRAF fault means that the cell receives too many signals to divide. So the melanoma cells divide too quickly and can grow rapidly. Researchers are looking into drugs that block the BRAF skin cancer protein. These groups of drugs are called BRAF inhibitors or pyridoimidazolones. PLX4032 is a new and experimental drug and is a type of BRAF inhibitor. A phase 3 trial called BRIM3 compared vemurafenib (PLX4032) with the chemotherapy drug dacarbazine (DTIC) for people with advanced melanoma who hadn't had any other treatment. This trial found that the cancer either stopped growing or shrunk in nearly half the people (50%) having vemurafenib compared to 1 in 20 people (5%) having dacarbazine. These were interim results and the researchers decided to stop the trial and the people having dacarbazine were able to start on the vemurafenib. We have information about PLX4032 and melanoma in the question and answer section of CancerHelp UK.

MEK inhibitors

Doctors are also looking at a new type of drug called ‘MEK’ inhibitors. Results from a meeting in June 2010 show that MEK inhibitors might be a useful treatment for advanced melanoma. But larger trials need to be done to see how useful the treatment is long term. AZD6244 is a type of MEK inhibitor. A trial looked at AZD6244 and dacarbazine for advanced melanoma in people with a BRAF gene fault. This trial is now closed to recruitment and we are waiting for the results.

Drugs that block cell growth

Imatinib and nilotinib are 2 different types of biological therapy called tyrosine kinase inhibitors. This means they block chemicals (enzymes) that a cancer needs in order to grow. A small group of melanomas have a receptor on the cell called CD117. When this is over expressed it is also a type of mutation. Doctors call these types of cells c-kit positive. In melanoma, c-kit positive cells are usually found in people with rarer types of melanoma that are found in the mucosal tissue (anus or vaginal). Or in melanomas which are found on hands and feet (acral melanomas ).

Very early trials suggest that imatinib and nilotinib can help people with mucosal or acral melanoma that are c-kit positive. Imatinib and nilotinib block c –kit. So these drugs work best on c-kit positive cells. The NICAM trial is looking at nilotinib for people with advanced mucosal or acral melanoma with c-kit positive cells. The aim of the trial is to see how well the treatment works for this group of people.

A phase 2 study is looking at whether bortezomib and an epilepsy drug could be a treatment for melanoma. Bortezomib (Velcade) is a type of biological therapy called a proteasome inhibitor. It blocks cancer cells from breaking down proteins that the cell doesn't need so the cell dies. Researchers know that the anti epilepsy drug sodium valproate blocks enzymes called histone deacetylases, which cells need to grow and divide. Early research into using drugs like sodium valproate for cancer has shown promising results. This study is to find out how small doses of bortezomib (Velcade) and the epilepsy drug sodium valproate work in people with melanoma. 

Vaccines

Cancer vaccines are a fairly new area of research. Vaccines may help your immune system to kill the cancer cells. The phase 3 trials that have been done so far have had disappointing results. But research into these vaccines is continuing.

One trial is looking at a treatment called OncoVEX GM-CSF for people with advanced melanoma that cannot be removed with surgery. The treatment uses a form of the cold sore virus that has been changed so that it is not harmful to normal cells but destroys cancer cells. GM-CSF is a growth factor that encourages the immune system to recognise and attack cancer cells. Doctors want to find out if the virus will kill cancer cells and if GM-CSF boosts the immune system to help fight cancer. 

The DERMA trial is looking at a type of vaccine called MAGE-A3 ASCI. Early trials showed that this vaccine slowed the growth of advanced melanoma. The researchers in the DERMA trial want to find out if it can delay or stop melanoma coming back after surgery. The vaccine teaches the immune system cells to recognise a protein called MAGE-A3 found on melanoma cells. This should help the immune system to find and kill any melanoma cells left after the surgery. The trial also aims to learn more about the side effects of the vaccine. 

There is a whole section about melanoma vaccines in this section of CancerHelp UK.

Gene therapy

This is one of the newer approaches to cancer treatment and is in the very early stages of clinical trials in the USA and UK. It really is early days. We are a long way from having gene therapy treatment for melanoma. We don't yet know if it will work at all.

By studying how changes in these genes cause normal cells in the skin to become cancerous, scientists aim to eventually develop gene therapy so that damaged genes in the cancer cells can be replaced with normal ones.

One example of gene therapy is with a drug called Augmerosen. This drug can stop cells from making a protein found in many melanoma cells. This protein stops the melanoma cells dying off, as normal cells eventually would. In very early studies, people with advanced melanomas were given Augmerosen with a chemotherapy drug called dacarbazine (DTIC). In some people the melanomas shrank. This is a very early phase trial and we don't know how effective this drug is in treating melanoma.

There is general information about gene therapy in the biological therapy section.

Tumour necrosis factor (TNF)

This is another biological therapy that has been tried, along with chemotherapy, in regional limb perfusion. Regional limb perfusion is a way of giving drug treatment to just one arm or leg that is affected by melanoma. It is usually used for melanoma that has come back in the same limb after it was first treated. More trials are needed before we know if it will help people with melanoma.

Your doctors may suggest chemotherapy for melanoma

• If your melanoma has come back
• If your melanoma is too advanced for surgery when it is diagnosed

Doctors have also used chemotherapy after surgery to try to lower the risk of the cancer coming back (adjuvant treatment). So far, there is no real evidence from research that adjuvant chemotherapy is helpful in stopping melanoma from coming back.

Dacarbazine (DTIC) has been tested more than any other chemotherapy drug for melanoma that has spread. It has had some success in controlling the melanoma for a time. Dacarbazine (DTIC) is usually the first choice of doctors using chemotherapy to treat melanoma.

A newer chemotherapy drug called temozolomide (Temodal) has had some success in treating brain tumours. A trial called EORTC 18032 compared temozolomide with dacarbazine for advanced melanoma. But the trial found that having higher dose temozolomide more frequently than the standard dose was no better than dacarbazine.

One trial is testing a new drug called Hyd-Sulfate (AZD6244) with the chemotherapy drug dacarbazine. AZD6244 is a type of drug called a MEK inhibitor and it works by blocking growth signals. MEK stands for mitogen activated protein kinase. It is a protein that sends signals to cells telling them to divide and grow. Researchers hope that AZD6244 will reduce the amount of MEK and slow down or stop the growth of cancer. The trial is for people with advanced melanoma whose melanoma cells have a change to a gene called BRAF. About half of people who have melanoma have a BRAF gene change. The researchers want to see if AZD6244 and dacarbazine chemotherapy is better than dacarbazine alone. The trial has closed and we are waiting for the results. 

The DOC-MEK trial is looking at docetaxel (Taxotere) chemotherapy with or without AZD6244. This trial is for people with advanced melanoma whose cells do not have a change in the BRAF gene. Doctors hope that using AZD6244 with docetaxel may work better than docetaxel alone.

You can find details of these trials on our clinical trials database. Type AZD6244 into the search box.