KRAS Testing

Medical Solutions™ is now offering KRAS mutation detection on DNA extracted from paraffin-embedded clinical material. The test includes a histopathology review of the sample to ensure tumour tissue is present.

Recent studies in non small cell lung cancer and colorectal cancer show that activating mutations of the gene encoding the signalling molecule KRAS are likely to give rise to resistance to:

• small molecule drugs e.g. (erlotinib; gefitinib) and
• antibody treatments e.g. (cetuximab, panitumumab) targeted at the Epidermal Growth Factor Receptor (EGFR)

This is because KRAS lies downstream in the EGFR signalling pathway and therefore, if it is continuously active based upon the presence of a mutation in the KRAS gene, inhibition of EGFR by the drugs listed above will be ineffective.

Testing for KRAS activating mutations may therefore offer further refinement to the treatment decision-making process, separating patients according to likely response to these agents. Serial sections are cut from the paraffin block and DNA extracted. Mutations are then detected using assays that can detect very low levels of mutant DNA in a background of wild type genomic DNA.

A positive result in this test indicates the presence of an activating mutation in the KRAS gene, and suggests that this patient is unlikely to respond favourably to treatment with small molecule or antibody treatment targeted at EGFR.