Cancer growth blockers
Cancer growth blockers are also called cancer growth inhibitors. They are a type of targeted cancer drug.
Our body makes chemicals called growth factors that control cell growth. Cancer growth blockers work by blocking the growth factors that trigger cancer cells to divide and grow.
There are many types of cancer growth blockers that work in different ways.
What are growth factors?
Growth factors are chemicals produced by the body that control cell growth. There are many different types of growth factors and they all work in different ways.
Some growth factors tell cells what type of cells they should become (how they should specialise). Some make cells grow and divide into new cells. Some tell cells to stop growing or to die.
Growth factors work by binding to receptors on the cell surface. This sends a signal to the inside of the cell, which sets off a chain of complicated chemical reactions.
Types of growth factor
There are a number of different growth factors. These include:
- epidermal growth factor (EGF) – controls cell growth
- vascular endothelial growth factor (VEGF) – controls blood vessel development
- platelet derived endothelial growth factor (PDGF) – controls blood vessel development and cell growth
- fibroblast growth factor (FGF) – controls cell growth
Each growth factor works by attaching to the corresponding receptor on the cell surface. For example, EGF binds to epidermal growth factor receptor (EGFR).
Tyrosine Kinases are chemical messengers (enzymes) used by cells to control how they grow and divide. They act like an ‘on-off’ switch. When the growth factor attaches to the outside of the cell it switches the tyrosine kinase ‘on’. This signals the cell to divide.
What are cancer growth blockers?
A cancer growth blocker is a targeted drug that blocks the growth factors that trigger cancer cells to divide and grow. Scientists are looking at different ways of doing this such as:
- lowering levels of the growth factor in the body
- blocking the growth factor receptor on the cancer cell
- blocking the signals inside the cell that start up when the growth factor triggers the receptor
Most of these treatments work by blocking the signalling processes that cancer cells use to divide.
Cancer cells are often very sensitive to growth factors. So if we can block them, we can stop some types of cancer from growing and dividing. Scientists are developing different inhibitors for the different types of growth factors.
It isn't easy to group targeted therapies into different types because the groups often overlap. This can be confusing. For example, some cancer growth blockers stop the growth of blood vessels to the growing cancer. So they are also working as an anti angiogenic drugs. Some cancer growth blockers are also a monoclonal antibody.
Types of cancer growth blockers
There are many different types of cancer growth blockers. They can be grouped according to the types of chemical that they block. There are some examples below.
Tyrosine kinase inhibitors (TKIs) block chemical messengers (enzymes) called tyrosine kinases. Tyrosine kinases help to send growth signals in cells, so blocking them stops the cell growing and dividing.
Cancer growth blockers can block one type of tyrosine kinase or more than one type. TKIs that block more than one type of tyrosine kinase are called multi TKIs.
Examples of TKIs include:
- axitinib (Inlyta)
- dasatinib (Sprycel)
- erlotinib (Tarceva)
- imatinib (Glivec)
- nilotinib (Tasigna)
- pazopanib (Votrient)
- sunitinib (Sutent)
You take these TKIs as tablets or capsules, usually once or twice a day.
Proteasomes are tiny, barrel shaped structures found in all cells. They help break down proteins the cell doesn't need into smaller parts. The cell can then use them to make new proteins that it does need.
Drug treatments that block proteasomes from working are called proteasome inhibitors. They cause a build up of unwanted proteins in the cell, which makes the cancer cells die.
Doctors use proteasome inhibitors to treat myeloma. Examples include:
- bortezomib (Velcade)
- carfilzomib (Kyprolis)
- ixazomib (Ninlaro)
mTOR is a type of protein called a kinase protein. It can make cells produce chemicals (such as cyclins) that trigger cell growth. It may also make cells produce proteins that trigger the development of new blood vessels. Cancers need new blood vessels in order to grow.
In some types of cancer mTOR is switched on, which makes the cancer cells grow and produce new blood vessels. mTOR blockers (inhibitors) can stop the growth of some types of cancer.
mTOR inhibitors include:
- temsirolimus (Torisel)
- everolimus (Afinitor)
PI3Ks are a group of closely related kinase proteins. Their full name is phospho inositide 3 kinases.
They do a number of different things in cells. For example, they act like switches in the cell turning on other proteins such as mTOR (see above). Switching on PI3Ks might make cells grow and multiply, or trigger the development of blood vessels, or help cells to move around.
In some cancers PI3K is permanently switched on, which means that the cancer cells grow uncontrollably. Researchers have been developing new treatments that inhibit PI3K. For example, idelalisib (Zydelig) is now available as a treatment for some people with chronic lymphocytic leukaemia (CLL).
Histone deacetylase inhibitors are also called HDAC inhibitors or HDIs.
They block the action of a group of enzymes that remove chemicals called acetyl groups from particular proteins. This can stop the cancer cell from using some genes that would help it to grow and divide. This might kill the cancer cell completely.
HDACs are a newer type of cancer growth blocker. Panobinostat is an example of an HDAC. It is a treatment for myeloma. Researchers are looking at some other HDACs including:
Hedgehog pathway blockers are drugs that target a group of proteins known as the hedgehog pathway. In the developing embryo, these proteins send signals that help cells to grow in the right place and in the right way.
The hedgehog pathway can also control the growth of blood vessels and nerves. In adults, hedgehog pathway proteins are not usually active. But in some people, changes in a gene switch them on. Hedgehog pathway blockers are designed to switch off the proteins and stop the growth of the cancer.
Vismodegib (Erivedge) is an example of a hedgehog pathway blocker. It is used in some situations to treat people with basal cell skin cancer that has spread.
BRAF inhibitors directly block a protein called BRAF. BRAF is a chemical messenger (enzyme) that controls how cells grow and send signals.
Some cancers have a change (mutation) in the BRAF gene. This genetic change makes the cancer cells produce too much BRAF protein, which can make cancer cells grow. BRAF inhibitors block the BRAF proteins and can stop cancer cells growing.
BRAF inhibitors are a treatment for advanced melanoma. Examples include:
- vemurafenib (Zelboraf)
- dabrafenib (Tafinlar)
- encorafenib (Braftovi)
The BRAF protein can affect other proteins, such as MEK, which makes cancer cells divide and grow in an uncontrolled way. MEK inhibitors are another type of targeted cancer drug. They work by blocking the MEK protein, which slows down the growth of cancer cells. Two MEK inhibitors for melanoma are:
- trametinib (Mekinist)
- binimetinib (Mektovi)
You usually have a BRAF inhibitor with a MEK inhibitor. This is because having the combination of both drugs can work better.
How you have them
Cancer growth blockers are often tablets which you swallow once or twice a day.
You might have some cancer growth blockers as an injection under the skin (subcutaneous injection), or through a drip (infusion) into a vein.
How often you have treatment and how many treatments you need will depend on:
- which drug you have
- the type of cancer you have
Before you have some types of cancer growth blockers you might need to have tests using some of your cancer cells or a blood sample to find out whether the treatment is likely to work. These tests look for changes in certain proteins or genes.
Your cancer specialist can tell you if this applies to your treatment. This is not the case for all cancer growth blockers and you don’t always need this test.
To test your cancer cells, your specialist needs a sample (biopsy) of your cancer. They might be able to test some tissue from a biopsy or operation you have already had.
Possible side effects
All treatments can cause side effects. While there are general side effects for a type of treatment, they vary for each individual drug.
Tell your doctor or nurse if you have any of these effects. You may be able to have medicines to help to control them.
General side effects
In general, cancer growth blockers can cause:
- tiredness (fatigue)
- skin changes, such as rashes or discolouration
- a sore mouth
- loss of appetite
- low blood counts
- swelling of parts of the body, due to build up of fluid
Specific side effects
Some cancer growth blockers are more likely to cause some side effects and these can sometimes be serious. For example, some cancer growth blockers are more likely to cause a serious skin rash. Your team will tell you about this before your start treatment and what to do if you develop side effects.