Bowel adenocarcinomas arise through a series of mutations that occur over the space of many years, and results in the evolution of normal tissue to adenoma (polyp) to carcinoma (cancer) to metastasis.
AKT1 is mutated in 1.06% of bowel cancer patients.
Vistusertib and selumetinib are the most frequent therapies in bowel cancer trials with AKT1 mutations as inclusion criteria.
BRAF is mutated in 8.38% of bowel cancer patients.
Cetuximab and panitumumab are currently approved for use in patients with BRAF mutation in bowel cancer.
Cetuximab, vemurafenib, and irinotecan are the most frequent therapies in bowel cancer trials with BRAF mutations as inclusion criteria.
KRAS is mutated in 47.01% of bowel cancer patients.
Trametinib, cetuximab, and binimetinib are the most frequent therapies in bowel cancer trials with KRAS mutations as inclusion criteria.
NRAS is mutated in 3.99% of bowel cancer patients.
Trametinib, asn007, and gemcitabine are the most frequent therapies in bowel cancer trials with NRAS mutations as inclusion criteria.
PIK3CA is mutated in 14.49% of bowel cancer patients.
Extended release flucytosine, pi3k/mtor inhibitor ly3023414, and prexasertib are the most frequent therapies in bowel cancer trials with PIK3CA mutations as inclusion criteria.
PTEN is mutated in 3.86% of bowel cancer patients.
TP53 is mutated in 63.7% of bowel cancer patients.
Extended release flucytosine, ly3143921 hydrate, and sra737 are the most frequent therapies in bowel cancer trials with TP53 mutations as inclusion criteria.
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.
About half of metastatic 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.
• 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.
When should I be tested?
RAS testing is recommended as soon as you are diagnosed with 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.