KRAS protein has an important role in cell signalling. KRAS is situated inside the cell, where it is usually tethered to the cell membrane, close to the intracellular parts of certain receptors on the cell surface.
KRAS protein acts as an on/off switch for downstream signalling of these receptors inside the cell. Factors that trigger signalling pathways mediated by KRAS include Epidermal Growth Factor (EGF), which binds to Epidermal Growth Factor Receptor (EGFR) and activates it. This activation, mediated by KRAS, may have various effects for the cell, including cell proliferation.
The human KRAS protein is encoded by the KRAS gene. When the gene is not mutated, the protein functions normally. However, certain mutations in the KRAS gene result in the expression of KRAS protein that is constitutively active. This causes uncontrolled cell growth and proliferation – a hallmark of a cancer cell. Such KRAS gene mutations are often found in e.g. colorectal, pancreatic and lung cancer tumours, and are thus called oncogenic (cancer-causing).
Indeed, the oncogenic, mutated versions of KRAS explain the name of the protein: V-Ki-Ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS). In cancer, oncogenic KRAS mutations are most often found only in the tumour and are not inherited.
Some anti-cancer drugs target the EGFR pathway to block EGFR signalling, and thereby to block tumour growth and proliferation. These therapeutics include Cetuximab (Erbitux®, Merck Serono) and Panitumumab (Vectibix®, Amgen) for colorectal cancer, which act by inhibiting EGFR activation.
However, if the tumour has mutated and thus oncogenic, constitutively active KRAS, which acts as a downstream signalling mediator from EGFR, Panitumumab and Cetuximab will not work.
KRAS mutation testing in colorectal cancer
Approximately 40% of colorectal cancers have mutated KRAS. In order to ensure that anti-EGFR therapeutics are not prescribed to colorectal cancer patients who will not benefit, KRAS mutation testing is required before commencing Panitumumab or Cetuximab therapy.
The KRAS mutation test provided by Lab 21 detects oncogenic KRAS mutations with high sensitivity and specificity. Our test turnaround time is only 5 working days.
KRAS mutation testing for colorectal cancer is funded by pharmaceutical companies for certain patients.
Information for test processing
To request KRAS testing, the first point of contact is the dedicated Lab 21 Customer Services Team who handle:
- Test Requests and Customer Support
- Liaison with Sample Retention Sites for sample retrieval if required
- Reporting of the results
Lab 21 provides a KRAS mutation testing service from its accredited clinical laboratory using an accurate, CE-marked test method. Please provide sections of formalin-fixed, paraffin embedded (FFPE) tumour. Full requirements for sample preparation can be seen on the sample handling instructions.