How do targeted therapies for cancer work?

PARP inhibitors are quite a new type of targeted therapy. They work by stopping cancer cells from carrying out essential DNA repairs.

All cells gather DNA damage as they divide and grow. However, cancer cells often accumulate more DNA damage than healthy cells, and they can also find it harder to repair that damage too. This is a recognised ‘weak spot’ for cancer, and researchers are working hard to find ways to exploit this important vulnerability.

One way is to target a group of proteins that are heavily involved in DNA repair, called PARP proteins. Cancer cells can become very reliant on PARP proteins, and so are especially vulnerable to drugs that are designed to block these proteins from working (called PARP inhibitors). When PARP protein activity is blocked, cancer cells find it very hard to repair damaged DNA, and become more likely to die. 

PARP inhibitors have only been available to patients for the last 10 years, but research funded by our supporters for many years before that helped to bring the first PARP inhibitor, called olaparib, to patients.

Monoclonal antibodies are special proteins that are engineered in a lab. These proteins can recognise and stick to other proteins, including proteins that coat cancer cells . Monoclonal antibodies work in many different ways, but they all aim to stop the cancer cell from growing and surviving:

• Some monoclonal antibodies work by stopping the cancer cell from receiving the signals it needs to divide and grow. They bind to and block special receptor proteins on the cancer cell surface that are used to receive these signals, and prevent important messages from getting through.
• Other types of monoclonal antibody work by stopping the cancer cell from hiding from our immune system. One way they might do this is by sticking to the cancer cell so that our immune system can easily spot it and attack. Because these monoclonal antibodies are essentially helping our immune system to find and target cancer cells, they are also classed as a type of
• Some types of monoclonal antibody even behave like tiny delivery vans, carrying active drug molecules directly to the cancer cell.

Worldwide Cancer Research scientist Dr Jo Perry in New Zealand is currently using your donations to try and develop a new type of monoclonal antibody. Dr Perry and her team are designing the antibody to block growth hormone receptors on the cancer cell, and stop the cancer cell from receiving signals to grow. The researchers believe that using this type of antibody in combination with radiotherapy could help to make radiotherapy work better, and reduce the development of treatment resistance for some types of cancer. 

Antiangiogenic therapies block the proteins and signals that cancer cells use to grow blood vessels (angiogenesis). All tumours need a good blood supply as they grow, and killing off the blood vessels that feed a tumour can be one way to slow the speed of its growth, and reduce the chance of it spreading.

Some types of monoclonal antibody can work as antiangiogenic therapies.  Bevacizumab, which is used to treat various cancers, is an example of an antiangiogenic monoclonal antibody. It works by blocking VEGF, a molecule that is important for cancer blood vessel growth.

Cancer growth inhibitors are a broad group of targeted therapies which all work to stop cancer cells receiving and acting on growth signals. These signals are usually delivered in the form of specialised molecules, and some cancer growth inhibitors work by stopping these molecules from activating special receptors on the surface of the cancer cell.

Other types of growth inhibitors work inside the cell, targeting proteins which are involved in cancer cell division and growth. Various types of drugs and monoclonal antibodies can act as cancer growth inhibitors.

BRAF inhibitors and MEK inhibitors, which are sometimes used to treat some forms of melanoma, are both cancer growth inhibitors. They work to block BRAF and MEK proteins in the cancer cell. Both of these proteins are part of a network of molecules that cause cancer growth, and that sometimes become overactive in cancer cells as a result of DNA changes.