Targeted Therapy

What is targeted therapy?

Targeted therapy is a way of treating cancer using drugs designed to target cancer cells, with minimal effect on normal cells. This is achieved by blocking specific molecular targets, usually altered genes or proteins specific to cancer cells, that are driving cancer cells' growth. These molecular alterations can occur on the surface of cancer cells, inside the cells or in the area around the tumour. This tailored form of treatment is sometimes called precision medicine as it targets specific changes or substances in cancer cells.

The poster child of targeted therapy is Imatinib, a drug that shuts down the activity of an abnormal gene, known as the BCR-ABL gene, which is found in chronic myeloid leukaemia (CML). The development and subsequent use of Imatinib has transformed the treatment of CML, changing it from a routinely fatal leukaemia to a disease where over 95% of the patients survive more than 5 years.

Since then, a better understanding of various cancers and the discovery of new drugs have rapidly expanded the targeted therapy options for many cancers. Most patients who receive targeted therapy also undergo other forms of treatment such as surgery, chemotherapy or radiotherapy to achieve better results.

Who is suitable to receive targeted therapy?

Targeted therapy has found success in many cancer types, including lung, breast, colorectal, skin and leukaemia. However, it is only suitable for some cancers, as not all cancers have molecular targets. Even within the same type of cancer, the molecular targets may differ from one patient to another. For that reason, an important step in assessing whether a patient is suitable for targeted therapy is molecular testing for specific actionable gene or protein alterations. These tests look for the existence of specific genes or changes in protein structure on the cancer cells that can be acted upon by medications. This will allow patients to be matched with the most effective treatment.

You may need to undergo surgery or biopsy – a procedure where your doctor removes a piece of the tumour for testing. Alternatively, in advanced cancers, cancer cells may shed fragments of abnormal cancer cells DNA into blood circulation. These can be captured and analysed for molecular alterations. Molecular testing has improved significantly in recent years. Multiple alterations can be tested concurrently on small specimens, to produce results within a shorter timeframe.

Your doctor will inform you whether targeted therapy is suitable for you.

How does targeted therapy work?

Different types of targeted therapy act on different molecular targets associated with cancer. They stop the cancer cells from growing by:

• Interrupting the growth signals that tell cancer cells to grow and divide
• Altering proteins within cancer cells that lead to cells death
• Attaching onto cancer cells and delivering anticancer treatment directly to the cancer cells to kill them
• Starving the cancer cells of nutrients leading to cells death
• Attaching onto the cancer cells to allow for an easier “search-and-destroy” effort by the immune system
• Stopping the formation of new blood vessels to feed growing cancer cells

Some types of targeted therapy work in more than one way to stop cancer growth.

How is targeted therapy given?

Targeted therapy can be given in different ways:

• by injection or infusion into a vein (drip)
• by injection under the skin
• as tablets or capsules

There are specific ways each treatment is administered. If your doctor decides to prescribe oral targeted therapy, you should take note of the dosage, frequency of administration, timing of administration with regards to food and whether there is a routine treatment break in each cycle. You should discuss with your cancer team about any concomitant usage of other medications and supplements even for unrelated health conditions. Some treatments may require routine supportive medications such as moisturising cream or antidiarrheal medicines.

Safety of targeted therapy

You need to take certain precautions when receiving targeted therapy. This is to protect your family and friends from unnecessary exposure to cancer drugs.

If you are given oral targeted therapy to take at home, you should not let your family members or friends come into contact with the medication. Sometimes this may also include contact with your body fluids while you undergo treatment (or for a time after completing treatment).

Examples of targeted therapy

Targeted therapy is now used to treat many kinds of cancer. A few examples are shown below:

• Trastuzumab targets tumours with mutations in the ERBB2 gene, also known as the HER2 gene, which causes it to make too many copies of itself. Trastuzumab is used to treat HER2-positive cancers including breast, stomach and oesophagal cancers.
• Osimertinib works on lung cancer cells that have mutation in epidermal growth factor receptor (EGFR) protein that drives cancer growth.
• Bevacizumab is used to treat many different cancers, including colon, lung, brain, and kidney cancers. It works by blocking the formation of new blood vessels.
• Bortezomib is used to treat blood cancer (multiple myeloma) by blocking the breakdown of a specific protein called the proteasomes. The subsequent build-up of proteasomes in the cell causes death.
• Olaparib is a poly ADP-ribose polymerase (PARP) inhibitor. Cancer cells with DNA repair mutations cannot repair any DNA damage in the presence of PARP inhibitor, leading to cells death. Olaparib is used to treat breast, ovarian, prostate and pancreas cancer.
• Hormonal therapy is a type of targeted therapy designed to prevent estrogen or testosterone from binding to receptors that drive cancer growth. For example, drugs such as anastrozole, fulvestrant and tamoxifen are used in breast cancer, while abiraterone and enzalutamide are used in prostate cancer.

There are many types of targeted therapy. The potential side effects of targeted therapy depend on which targeted therapy drug you are given and the drug targets. Some targeted therapy has minimal side effects whilst others may lead to uncommon but serious problems. Side effects also vary from one person to another.

Side effects of targeted therapies may include:

• sensitivity to sunlight – your skin may become dry, red, or itchy
• skin rash that looks like acne
• tenderness and rash of the palms of the hands and soles of the feet (known as the hand-foot syndrome)
• fatigue
• decreased appetite
• nausea
• diarrhoea
• liver injury
• muscle, bone, and joint pain
• high blood pressure
• decreased numbers of certain cells in the blood
• bleeding or blood clots
• slow wound healing
• changes to the way the heart works

Some targeted therapies may have unique side effects not covered in the list above. Your doctors will advise and monitor you for these side effects.

It is important to note that not every person will experience every side effect and the type and severity of these side effects vary from patient to patient. Most of these side effects can be managed with supportive measures. In some cases, your doctor may reduce the dosage of your medications. Please monitor your condition and notify your cancer care team if unexpected side effects occur.

How long do targeted therapy side effects last?

Most side effects of targeted therapy such as rash, high blood pressure and diarrhoea improve soon after stopping drugs. Some uncommon but serious side effects such as blood clots and changes to heart function may have more long-term effects. Talk to your cancer care team if you have any concerns about side effects, and be sure to report all changes in side effects to them.

You may wish to complement your targeted therapy with herbal or dietary supplements but before you do so, you must discuss it with your doctor or pharmacist as some of these supplements may interact with your cancer therapy.

Certain supplements will affect the concentration of anticancer medication in your blood. This often happens because the supplement interferes with drug metabolism or modifies the action of some crucial enzymes.

For example, a popular supplement St. John’s Wort interacts with imatinib by increasing the drug clearance from the body. Taking these two together may reduce the effectiveness of imatinib.

Additionally, ginseng (Panax ginseng) has been shown to interact with imatinib, and possibly cause liver toxicity. Because ginseng has estrogenic effects, you should consult your doctor if you have hormone-sensitive cancers.