An important step towards personalised, targeted treatment for advanced bowel cancer

Targeted therapies 

The development of biological therapies, also known as targeted therapies, is an exciting step forward in the treatment of cancer as it may be possible to destroy cancer cells without damaging other healthy cells.
This is a relatively new field of research and many therapies are still experimental.
Targeted therapies are usually given in combination with other standard chemotherapy treatments.
These new drugs may:

• stop cancer cells from dividing and growing
• seek out cancer cells and kill them
• encourage the immune system to attack cancer cells
• alter the growth of blood vessels into the tumour
There is no simple way of grouping these therapies.
Some drugs are grouped according to the effect they have, for example: drugs that block cancer cell growth (called EGFR inhibitors) or drugs that block the growth of new blood vessels to the tumour (VEGF inhibitors).
Some of these drugs can also be called monoclonal antibodies because they target specific proteins on cancer cells.
New drugs are being developed which act in different ways and may have multiple modes of action.

What is RAS?

The RAS gene family – which includes KRAS, NRAS and HRAS - produces proteins (RAS proteins) that are involved in cell signalling. 
RAS proteins play an important role in the regulation of cell growth, cell division and cell death. 
Everyone has RAS genes because we need them for cells to grow normally. 
Normal RAS genes are also called 'wild-type' RAS genes.
Some people will develop an abnormal or 'mutated' version of the RAS gene.
Mutated RAS genes result in RAS proteins being locked into a permanently 'switched on' state.  Like a car with an accelerator that won't release and brakes that won't engage, cell growth and divisions become out of control and evade signals to die.
RAS mutations can also allow cells to resist available targeted therapies.
Bowel Cancer Australia Treatment KRAS 770
Human KRAS protein.  (Image by Sarangan Ravichandran, Ph.D., Frederick National Laboratory for Cancer Research).  Source: National Cancer Institute 

Why is RAS status important?

RAS status is important as it gives your oncologist the information they need to decide if adding a targeted therapy to your chemotherapy treatments may work for you.  It does not affect the way your chemotherapy is prescribed.
About half of advanced bowel cancers will have RAS 'wild-type' genes and about half will have 'mutated' RAS genes. 
Patients with 'wild-type' RAS genes may respond to treatments with the targeted therapies Erbitux (cetuximab) or Vectibix (panitumumab).  It is therefore important to know the RAS status of a cancer before your treatment commences.

Personalising (or tailoring) medical treatment according to your genetic make-up helps:

• avoid potential adverse effects from ineffective treatments
• avoid delay in seeking alternative treatments which may be effective
• reduce the costs of ineffective treatment

Patients with 'mutated' RAS genes are unlikely to benefit from Erbitux or Vectibix.
If this is the case, patients may still benefit from targeted therapies which work in a different way such as Avastin (bevacizumab).

What is RAS biomarker testing?

RAS testing is currently performed on a small sample of tissue taken from the cancer during a biopsy or surgery.
DNA from the cancer cells is extracted, purified and tested for known mutations on the RAS genes.
Until recently, testing was only available for specific mutations at a couple of sites on the KRAS gene.
However, new knowledge and improved testing has shown that additional mutations on the KRAS gene, and on the NRAS gene, are also implicated in cancer resistance to EGFR inhibitors.  In the near future, RAS tests may also be available via a blood test. 

Frequently asked questions
When should I be tested?
RAS testing is recommended as soon as you are diagnosed with advanced or metastatic bowel cancer. 
Do I need another biopsy or more surgery to provide the sample for testing?
Initial RAS testing can be performed on samples stored from the original surgery.  Those samples may have been frozen or fixed in formalin.
Will I only need one RAS test?
There is evidence that some people will develop acquired resistance to EGFR inhibitors.  A RAS test may need to be repeated if the treatment is no longer working and/or the cancer progresses.
Is RAS testing expensive?
RAS testing is reimbursed by Medical Benefits Scheme; Item No: 73338.

If you have recently been diagnised with advanced (metastatic) bowel cancer,
ask your doctor about a RAS biomarker test. 
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