Targeted therapy: precision cancer treatment based on the tumour's genetic profile

What targeted therapy is

The growth of many cancers is driven by changes – mutations, fusions or amplifications – in particular genes. These changes make certain proteins overactive and keep switching on cell division. Targeted drugs block those proteins or the signalling pathways they control.

There are two main groups:

• Small-molecule drugs – usually tablets that enter the cell and block enzymes, such as tyrosine kinase inhibitors. Their generic names often end in "-ib".
• Monoclonal antibodies – given into a vein or under the skin, they attach to proteins on the cell surface or in the blood. Their names end in "-mab". This group includes antibody-drug conjugates, which carry a chemotherapy agent directly to the cancer cell.

Targeted therapy is a core part of precision oncology, one of the fastest-moving areas of cancer treatment. It is different from immunotherapy, which does not attack the tumour directly but helps the immune system to do so.

Molecular testing comes first

Before a targeted drug is prescribed, the tumour must be shown to carry the relevant target. Tests include:

• Immunohistochemistry – staining tissue for proteins such as HER2, PD-L1 or hormone receptors.
• FISH – looking for gene amplification or fusion.
• Next-generation sequencing (NGS) – testing dozens or hundreds of genes in a single sample.
• Liquid biopsy – analysing tumour DNA in the blood when tissue is limited or when looking for the cause of resistance.

Inherited (germline) genetics can matter too: BRCA1/2 mutations, for example, may make a patient eligible for PARP inhibitors. See BRCA genetic testing.

Which cancers are treated with targeted drugs

The list keeps growing. Some drugs are approved regardless of where the cancer started – for example for NTRK fusions – whenever the target is present.

How treatment is given

Many targeted drugs are tablets taken daily at home, often for months or years for as long as they work and are tolerated. It matters to take them exactly as prescribed, at the same time each day, and not to stop without talking to your oncologist. Some interact with foods such as grapefruit, with antacids or with herbal products, so always tell your team what else you take.

Antibodies are given into a vein or under the skin in a day unit at set intervals. Targeted therapy may be used alone or combined with chemotherapy, hormone therapy or immunotherapy. Response is monitored with scans (CT or MRI) and regular blood tests.

Side effects

Targeted therapy is not side-effect free – the effects are simply different from classic chemotherapy and depend on the target:

• Skin – acne-like rash (with EGFR inhibitors), dryness, inflamed nail folds, hand-foot syndrome.
• Digestive – diarrhoea, nausea, mouth ulcers.
• Heart and circulation – high blood pressure and, rarely, reduced heart function (HER2 treatment is monitored with echocardiograms).
• Liver – raised liver enzymes, checked with blood tests.
• Other – fatigue, swelling, visual changes and, rarely but seriously, lung inflammation (pneumonitis).

Most effects can be managed with supportive treatment, a short break or a dose reduction. Do not stop the drug yourself – discuss every problem with your team.

Resistance – why a drug may stop working

Targeted therapy often controls cancer for a long time, but tumours frequently find a way around the blockade – a new mutation in the target or activation of another pathway – and the disease starts to progress again. At that point a repeat tissue or liquid biopsy can reveal the resistance mechanism and point towards the next targeted drug, a combination or chemotherapy. Molecular testing is therefore not a one-off event; it may be repeated as treatment goes on.

Some patients may also be eligible for clinical trials of new drugs – ask your oncologist whether a suitable trial is available.

Questions to ask your oncologist

Precision oncology moves so quickly that it makes sense for patients and families to take an active part in treatment discussions. Useful questions include:

• Has my tumour had molecular testing, and which genes were tested – single tests or a broad NGS panel?
• Was a change found for which an approved targeted drug exists?
• What is the aim of treatment – controlling the disease, shrinking the tumour before surgery, or lowering the risk of recurrence?
• Which side effects should I expect, and which need an urgent call?
• What happens if the drug stops working – will the biopsy be repeated?
• Am I eligible for a clinical trial?

Write the answers down or bring someone with you to the appointment. You are entitled to ask for copies of all your results.

When to see a doctor

Contact your oncology team straight away if you develop new or worsening breathlessness or cough, a fever, severe diarrhoea (more than four to six times a day), a blistering rash, chest pain, palpitations, swelling, yellowing of the skin or eyes, or a sudden change in vision. If you have been diagnosed with cancer and no molecular testing has been done, ask whether it is relevant in your case.

Targeted therapy abroad and in Türkiye

Some patients from Bulgaria and the rest of Europe go to large accredited hospital groups in Istanbul for broad tumour profiling (NGS panels) and a second opinion on targeted treatment options. Bear in mind that targeted therapy usually continues for months or years, so it must be clear how the drug and monitoring will be provided at home and whether the drug is approved and reimbursed in your country. Ask for a written report with the test results and recommendations. Organisers such as New City Clinic coordinate the hospital, doctor, hotel, transfers and interpreter. Read more in Cancer treatment in Türkiye.