Targeted therapy for childhood brain and spinal cord tumours

Targeted therapy uses drugs to target specific molecules (such as proteins) on cancer cells or inside them. These molecules help send signals that tell cells to grow or divide. By targeting these molecules, the drugs stop the growth and spread of cancer cells and limit harm to normal cells. Targeted therapy may also be called molecular targeted therapy.

Targeted therapy is sometimes used to treat childhood brain and spinal cord tumours. It may be used to:

• treat childhood brain and spinal cord tumours that don't respond to other treatments or come back (recur) after treatment
• treat some types of brain and spinal cord tumours with certain genetic changes

The following types of targeted therapy may be offered to treat childhood brain or spinal cord tumours. The healthcare team will use what they know about the cancer and about your child's health to plan the drugs, doses and schedules.

Monoclonal antibodies have been designed in a lab to recognize and lock onto particular protein markers on the surface of some cancer cells. They then stimulate the body's immune system to attack and destroy the cells they attach to.

Monoclonal antibodies can be used alone or in combination with chemotherapy or other targeted therapy drugs. The most common monoclonal antibody used to treat childhood brain and spinal cord tumours is bevacizumab (Avastin and biosimilars).

mTOR inhibitors block the mammalian target of rapamycin (mTOR). mTOR is a protein that regulates cell growth and reproduction. In some types of cancer, including brain tumours, mTOR is abnormal and causes cancer cells to keep growing and dividing. mTOR inhibitors block the action of mTOR, which can stop the growth of cancer.

mTOR inhibitors may be used for some types of brain and spinal cord tumours that come back after treatment or stop responding to treatment. mTOR inhibitors that may be used are:

• everolimus (Afinitor)
• sirolimus (Rapamune)

BRAF is a protein that sends signals in cells and helps with cell growth. Changes in the BRAF gene, called BRAF V600E, can be found in higher amounts in some types of brain tumours. Cancer cells that have changes to this gene are called BRAF V600E positive (BRAF V600E+).

Some types of brain and spinal cord tumours that come back after treatment or don't respond to other treatments and are BRAF V600E positive may be treated with:

• dabrafenib (Tafinlar)
• a combination of dabrafenib and trametinib (Mekinist)
• vemurafenib (Zelboraf)

MEK inhibitors control the growth of brain tumours by blocking the MEK protein. Since the MEK protein is normally turned on (activated) by the BRAF protein, MEK inhibitors are another way to treat brain tumours with BRAF gene mutations.

Trametinib (Mekinist) is a MEK inhibitor that is often given in combination with the BRAF inhibitor dabrafenib (Tafinlar).

Mutations in the neurotrophic tyrosine receptor kinase (NTRK) gene can cause too much cell growth and lead to abnormal cells and cancer. Sometimes this mutation is found in brain and spinal cord tumours. Cancer cells that have changes to this gene are called TRK-fusion positive.

Some types of brain and spinal cord tumours that come back after treatment or don't respond to other treatments and are TRK-fusion positive may be treated with:

• larotrectinib (Vitrakvi)
• entrectinib (Rozlytrek)

Side effects of targeted therapy will depend mainly on the type of drug or combination of drugs, the dose, how it's given and your child's overall health. Talk to your child's doctor or pharmacist about what side effects to expect.

Tell the healthcare team if your child has side effects that you think are from targeted therapy. The sooner you tell them of any problems, the sooner they can suggest ways to help your child.

Other side effects can develop months or years after treatment for childhood brain and spinal cord tumours. Find out more about late effects of treatments for childhood brain and spinal cord tumours.

Find out more about targeted therapy. To make the decisions that are right for your child, ask the healthcare team questions about targeted therapy.

Details on specific drugs change regularly. Find out more about sources of drug information and where to get details on specific drugs.