Clinical Information

Targeted cancer therapies are defined as antibody or small molecule drugs that block the growth and spread of cancer by interfering with specific cell molecules involved in tumor growth and progression. Multiple targeted therapies have been approved by the US Food and Drug Administration for treatment of solid tumor malignancies. Molecular genetic profiling is often needed to identify targets amenable to targeted therapies and to minimize treatment costs and therapy-associated risks.

One of the most common somatic alterations in colorectal cancer (CRC) and non-small cell lung cancer (NSCLC) is the presence of activating variants in the protooncogene KRAS. KRAS is recruited by ligand-bound (active) epidermal growth factor receptor (EGFR) to initiate the signaling cascade induced by the RAS/MAPK pathway. Because altered KRAS constitutively activates the RAS/MAPK pathway downstream of EGFR, agents such as cetuximab and panitumumab, which prevent ligand-binding to EGFR, do not appear to have any meaningful inhibitor activity on cell proliferation in the presence of altered KRAS. Current data suggest that the efficacy of EGFR-targeted therapies in CRC and NSCLC is confined to patients with tumors lacking KRAS mutations. An exception is the KRAS G12C variant that is targetable with variant-specific inhibitors.

This test uses DNA extracted from tumor tissue to evaluate for the presence of KRAS (G12A, G12C, G12D, G12R, G12S, G12V, G13D, Q61K, Q61L, Q61R, Q61H, and A146T) variants. A positive result indicates the presence of an activating KRAS mutation and can be useful for guiding the treatment of patients with CRC and NSCLC.