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Melanoma research

Men and women discussing melanoma skin cancer

This page of the melanoma section is about research into the causes, prevention and treatments of melanoma skin cancer. There is information about

 

A quick guide to what's on this page

Melanoma research

All treatments must be fully researched before they can be adopted as standard treatment for everyone. This is so that we can be sure they work better than the treatments we already use. And so we know that they are safe.

First of all, treatments are developed and tested in laboratories. Only after we know that they are likely to be safe to test are they tested in people, in clinical trials. Cancer Research UK supports a lot of UK laboratory research into cancer and also supports many UK and international clinical trials.

Researchers are looking into

 

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Why we need 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
 

The research process

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. Cancer Research UK supports a lot of UK laboratory research into cancer.

Tests in patients are called clinical trials. Cancer Research UK supports many UK and international clinical trials.

Our 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 for melanoma, visit our searchable database of clinical trials. 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. The database also has information about closed trials and trial results.

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.

Here is a video on experiences of taking part in a clinical trial:

View a transcript of the video (Opens in a new window) 

 

Prevention and detection

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

You can find detailed information on melanoma in our clinical trials database.

National skin cancer prevention campaigns

Cancer Research UK has worked with the Department of Health to develop a national skin cancer prevention awareness campaign. The campaign called SunSmart was launched in March 2003. You can find lots of information about how to protect your skin from the sun in the  about melanoma section. You can also get information on Cancer Research UK's SunSmart pages.

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 don't 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 skin cancer questions and answers section.

Using scanners to detect melanoma

The MoleMate trial looked at whether a new type of hand held scanner helped GPs to tell the difference between normal moles and melanomas. The scanner was linked to a computer which analysed the moles and gave a report on whether the mole could be a melanoma. The researchers hoped using the scanner would reduce the number of people who are unnecessarily referred to a specialist. Both patients and doctors thought very positively about the MoleMate system. But from the results of this trial, the researchers concluded there was no evidence that using the system improved the appropriateness of referrals for suspected melanoma.

Another study looked at a new system called a Skin Analyser that takes detailed pictures and shows the texture of abnormal areas of skin. Researchers used 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 compared this with a standard way of diagnosing melanoma, using SIAscopy (hand held scanner test) and physical examination. The study team found that the Skin Analyser was more reliable that the standard way of diagnosing melanoma. You can read the results of the Skin Analyser study on our clinical trials database.

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 becoming cancerous. Scientists are using this information to develop new treatments for skin cancers.

A study is looking into the genetic changes that cause skin cancer. The researchers are collecting samples of tissue and blood from people diagnosed with melanoma and non melanoma skin cancer of the head and neck. They will use these samples to identify changes in genes that may have caused the cancer, and to identify how the body's immune system responds to the cancer.

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.

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

There is a study looking into lifestyle factors, such as how people live, what they eat, and how much time they spend in the sun after they have been treated. Researchers want to see if any of these factors might increase the risk of the melanoma coming back. This study is also looking at the genes of people with melanoma, to find out if any of these affect the risk of recurrence. This trial has now closed and we are waiting for the results.

 

Research into surgery for melanoma

When removing melanoma with surgery doctors sometimes 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. This trial has now closed and we are waiting for the results. 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 straight away.

The MELAMAG study is looking at using magnetic tracers, instead of radioactive tracers, to find the sentinel lymph nodes in people with melanoma. The researchers also want to find out more about the lymph vessels and the sentinel lymph nodes. They will use MRI scans to do this. This is called an MRI sub study. This study has now closed and we are waiting for the results.

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 research

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

You can find out about biological therapy trials for melanoma on our clinical trials database. If you want to see all the trials, tick the boxes for closed trials and trial results.

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 have used interferon treatment to try to prevent this. Interferon is made naturally as part of the body's immune response. It is a type of immunotherapy. Trials so far show that interferon only helps a few people and can cause side effects that lower people's quality of life. So it is not standard treatment. But doctors are trying to find out whether giving interferon in different ways can help.

Talimogene

Talimogene laherparepvec is a new type of biological therapy drug developed to treat melanoma that has spread beyond the area in which it first started. It is a type of immunotherapy. It is injected into the areas of melanoma to help to destroy them. It also makes the cells release a type of natural body protein called GM-CSF that triggers the immune system to destroy melanoma cells elsewhere in the body. An American phase 3 trial reported early results in November 2013. It involved 400 patients with stage 3 or 4 melanoma. Two thirds of the patients had talimogene and one third had a control treatment with GM-CSF.

Patients who had talimogene lived on average for more than 23 months. People who had GM-CSF lived on average for 19 months. The study is continuing to follow up the patients involved and will release more results in 2014. The most common side effects were tiredness, inflamed areas of skin (cellulitis), chills and high temperatures.

Ipilimumab

Trials show that a monoclonal antibody called ipilimumab can help some people with advanced melanoma to live longer. Some types of monoclonal antibody activate the immune system to seek out and destroy melanoma cells in the body.  The CA184024 study found that having ipilimumab with dacarbazine chemotherapy for stage 3 and 4 melanoma increased the length of time people lived after treatment. 

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 ipilimumab for children and young people who have melanoma that can’t be removed with surgery.

A phase 3 trial is looking at a new drug called MK3475 for people with advanced melanoma. The researchers are comparing 2 different doses of MK3475 with ipilimumab. They want to find out how well MK3475 works, which dose works best, and how it affects people's quality of life.

Bevacizumab (Avastin)

This is a treatment for advanced bowel cancer, and has also been used for other cancers. Bevacizumab (Avastin)  is another monoclonal antibody.The AVAST-M trial wanted to find out if bevacizumab after surgery for high risk melanoma helped stop or delay it from coming back. After an average follow up of 2 years, the trial team found that bevacizumab did increase the amount of time it took for melanoma to come back after surgery. But there was no difference in how long people lived. The trial team will continue to follow up the people who took part in the trial to find out if there is a difference in survival at 5 years after surgery. The researchers are also looking for substances in the blood (biomarkers) that could help doctors tell in advance who may benefit most from having bevacizumab after surgery.

Nivolumab

The CA209037 trial is looking at a new monoclonal antibody called nivolumab for advanced melanoma. The researchers are comparing this drug with the chemotherapy drugs doctors already use to treat advanced melanoma. The researchers want to find out if nivolumab is better than chemotherapy in this situation and to learn more about the side effects. The CA209067 trial is comparing nivolumab with ipilimumab for melanoma that can't be removed or has spread to other parts of the body.

Intetumumab (CNTO 95)

This is another type monoclonal antibody. Research is looking at how well intetumumab or CNTO 95 works in advanced melanoma. A small international trial using intetumumab for advanced melanoma combined it with the chemotherapy drug dacarbazine (DTIC). This research 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.

Dabrafenib

Dabrafenib stops cells producing the BRAF protein so this treatment can slow or stop the growth of the cancer. About half of all melanoma skin cancers make too much BRAF protein due to a change in the BRAF gene. The BRAF protein makes cells grow and divide. This means that the melanoma cells divide too quickly and can grow rapidly. Dabrafenib (Tafinlar) is a treatment for melanoma that has spread or can't be removed with surgery. 

A trial is looking at dabrafenib and trametinib for advanced melanoma. Trametinib is another type of biological therapy called a MEK inhibitor. Researchers want to compare dabrafenib and trametinib with dabrafenib on its own, to find out which is better at treating advanced melanoma with the BRAF mutation.

The COMBI-AD trial is looking at dabrafenib and trametinib after surgery for melanoma. The researchers want to find out if having these 2 drugs after surgery helps to stop melanoma coming back, and to learn more about the side effects of this drug combination. This trial has now closed and we are waiting for the results.

Another trial is comparing dabrafenib and trametinib with vemurafenib for advanced melanoma with the BRAF mutation.

Vemurafenib (Zelboraf) is a type of BRAF inhibitor. Research shows that it can shrink advanced melanoma for some people and help them to live longer. We have information about vemurafenib on the biological therapy for melanoma page in this section.

MEK inibitors

If the BRAF gene is faulty, it affects a protein called mitogen activated protein kinase (MEK). MEK sends signals to cells telling them to divide and grow. Doctors are looking at new types of drug that block the MEK protein and are called MEK inhibitors. Hyd-Sulfate (AZD6244) is a type of MEK inhibitor. A trial is looking at AZD6244 and dacarbazine for advanced melanoma in people with a BRAF gene fault.

A trial compared the MEK inhibitor drug GSK1120212 with chemotherapy for melanoma that had spread. GSK1120212 is now called trametinib. The trial team found that trametinib was better than dacarbazine (DTIC) or paclitaxel (Taxol) chemotherapy for advanced melanoma with a change in the BRAF gene.

Another trial is looking at GSK1120212 with paclitaxel chemotherapy for advanced melanoma.

MEK162 is another MEK inhibitor. Researchers think it may help people who have melanoma with a change to the gene called NRAS. The aim of the NEMO trial is to see if MEK162 works better than dacarbazine for melanoma that cannot be removed with surgery or has spread.

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) called tyrosine kinases that a cancer needs in order to grow. Some melanomas have a receptor on the cell called CD117. When there is a lot of this receptor it is caused by a gene change (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 they are found 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 melanomas that are c-kit positive. 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. This trial has now closed and we are waiting for the results.

Vandetanib is another type of tyrosine kinase inhibitor. Doctors know that this drug can make cancer cells more sensitive to radiotherapy. The RADVAN trial is looking to see if using vandetanib with radiotherapy can improve treatment for melanoma that has spread to the brain. The researchers will also be looking at the side effects of having this drug with radiotherapy. This trial has closed and we are waiting for the results.

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

Researchers have been studying cancer vaccines in melanoma for some time. 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 different types of 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. 

The Ludwig study is looking at 2 new vaccines after surgery for melanoma. You have the vaccines as injections. Both of them use a protein called the NY-ESO-1 antigen, which is found on some cancer cells. The vaccines help the immune system to recognise this antigen and kill the cancer cells. In one injection, the protein is combined with something called ISCOMATRIX, which can stimulate the immune system. The other vaccine combines the protein with a virus that has been changed so that it can't cause disease. The trial aims to find out if these vaccines can stimulate an immune response and to learn more about how safe they are and what the side effects are.

There is a whole page about melanoma vaccines in this section.

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 genes make normal cells in the skin 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. It is also called oblimersen or Genasense. This drug can stop cells from making a protein found in many melanoma cells. The protein stops the melanoma cells dying off, as normal cells eventually would. An international phase 3 study has been looking at Augmerosen with a chemotherapy drug called dacarbazine (DTIC) for people with advanced melanoma. It will be a couple of years before the results are known. 

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

Tumour necrosis factor (TNF)

TNF is a type of 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.

 

Radiotherapy research for melanoma

If melanoma spreads to the brain it can't be cured. But radiotherapy can sometimes help to shrink a melanoma tumour in the brain that is causing symptoms. Some people have surgery to remove the melanoma tumour. Or they may have stereotactic radiotherapy, which targets radiotherapy very precisely at the tumour. 

A trial is looking at radiotherapy for melanoma that has spread to the brain. It is looking at giving radiotherapy to the whole brain (whole brain radiotherapy) after surgery or stereotactic radiotherapy. It wants to find out if having whole brain radiotherapy after surgery or stereotactic radiotherapy (or both) helps to delay the melanoma from coming back. It also wants to find out about the side effects of whole brain radiotherapy. Doctors don't know at the moment if this treatment is helpful or not.

 

Chemotherapy research for melanoma

Researchers are trying to find better ways of using chemotherapy for melanoma. Your doctors may suggest chemotherapy for melanoma

  • If your melanoma has spread to other parts of the body
  • 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 in some people. Dacarbazine (DTIC) used to be the first choice of doctors using chemotherapy to treat melanoma. But now, doctors tend to only use it if the melanoma tumour does not have the faulty BRAF protein. If the tumour does have a faulty BRAF protein, doctors usually offer vemurafenib as the first choice of treatment. 

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 a higher dose of temozolomide more frequently than the standard dose was no better than dacarbazine.

Electrochemotherapy

In some countries doctors are looking at using bleomycin chemotherapy combined with an electrical current. This is called electrochemotherapy. The chemotherapy may be given into a vein or injected into the area of the melanoma. This treatment is very experimental at the moment and we don't know whether it will be helpful for melanoma. We don't know of any trials using this treatment in the UK.

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Updated: 23 January 2014