Patient Mutation Status Is a Critical Concern in Cancer Drug Evaluation Study

The growing interest in personalized medicine and tailored therapy has led to increased cooperation between diagnostic and pharmaceutical companies.

A recent example is the decision by the drug developer Amgen (Thousand Oaks, CA, USA) to use the K-RAS Cancer Mutation Detection Kit manufactured by the molecular diagnostics company DxS (Manchester, UK) for the on-going evaluation of its chemotherapeutic agent panitumumab (Vectibix).

Panitumumab works to silence the K-RAS gene by binding to the extracellular domain of the EGFR (epidermal growth factor receptor) preventing its activation. This halts the cascade of intracellular signals dependent on this receptor. In patients with mutant K-RAS, signaling continues despite anti-EGFR therapy. Activated K-RAS is detected in approximately 40% of metastatic colorectal cancers. Multiple studies support anti-EGFR therapy being significantly more effective in patients with non- mutated KRAS.

The DxS test is highly selective and robust, detecting seven key mutations in the K-RAS gene. It employs a real-time PCR format combining proprietary allele specific PCR technologies. The assay can detect <1% of mutant in a background of wild type genomic DNA and has a limit of detection of 10 copies or below.

Preclinical research has long implicated the RAS oncogene in cancer biology, but now this research may be translated into patient management, said Dr. Roger M. Perlmutter, executive vice-president of Research and Development at Amgen. In the future, physicians may select treatment options specifically for patients whose tumors harbor the non-mutated KRAS gene.

Dr Stephen Little, CEO of DxS said, "We are very pleased that Amgen chose the DxS K-RAS mutation kit and have benefited from the excellent selectivity of the test to maximize the number of mutation-positive individuals correctly identified in the analysis of tumors samples from the Vectibix pivotal study. K-RAS genotyping of tumors should now be considered in patients with metastatic colorectal cancer being treated with or considered for Vectibix monotherapy.


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