Clinical Information

Lung cancer is the leading cause of cancer-related deaths in the world. Non-small cell lung cancer (NSCLC) represents 70% to 85% of all lung cancer diagnoses. Randomized trials have suggested that targeted agents alone or combined with chemotherapy may be beneficial. Because the addition of targeted therapy may lead to an increase in toxicity and cost, strategies that help to identify the individuals most likely to benefit from targeted therapies are desirable. Monoclonal antibodies against epidermal growth factor receptor (EGFR) represent a new area of targeted therapy for such patients. However, studies have shown that not all individuals with NSCLC respond to these EGFR-targeted molecules.

EGFR is a growth factor receptor that is activated by the binding of specific ligands (epiregulin and amphiregulin), resulting in activation of the RAS/MAPK pathway. Activation of this pathway induces a signaling cascade ultimately leading to cell proliferation. Dysregulation of the RAS/MAPK pathway is a key factor in tumor progression. Targeted therapies directed to EGFR, which inhibit activation of the RAS/MAPK pathway, have demonstrated some success in treating a subset of patients with NSCLC.

In NSCLC, one of the most frequently reported alterations in the EGFR-signaling pathway is the presence of a mutation in the proto-oncogene KRAS. KRAS is recruited by ligand-bound (active) EGFR to initiate the signaling cascade induced by the RAS/MAPK pathway. Because mutant KRAS constitutively activates the RAS/MAPK pathway downstream of EGFR, agents that prevent ligand-binding to EGFR do not appear to have any meaningful inhibitor activity on cell proliferation in the presence of mutant KRAS. Current data suggest that the efficacy of EGFR-targeted therapies in NSCLC is confined to patients with tumors lacking KRAS mutations. As a result, the mutation status of KRAS can be a useful marker by which patients are selected for EGFR-targeted therapy.

At this time, this test is for unknown and/or unidentified primary tumors, primary tumors other than colorectal, and metastatic lesions from a primary other than colorectal. Please refer to KRASC / KRAS Mutation Analysis, 7 Mutation Panel, Colorectal for KRAS testing in colorectal tumors.