Medical Laboratory Science
Cell and Molecular Biology
KRAS; Mutation; Non-small cell lung cancer; Sequencing; EGFR
The kirsten rat sarcoma viral oncogene (KRAS) is found to be one of the most common mutated genes in non-small cell lung cancer (NSCLC). Decades have passed and researchers are still faced with difficulties understanding how the KRAS oncogene works and ways that it can be inhibited to provide NSCLC patients with a better prognosis. The three most common molecular methods for detecting the presence of KRAS are circulating free DNA (cfDNA), Sanger capillary sequencing and next generation sequencing (NGS). The specificity and sensitivity for detecting KRAS mutants has markedly improved and continues to advance by reducing cost and amount of specimen needed. In many cases of NSCLC, epidermal growth factor receptor (EGFR) mutations are also found as frequently mutated. The discovery of an EGFR mutation is typically reflexed with KRAS testing since KRAS is found downstream of EGFR and tends to reduce the success of tyrosine kinase inhibitors used to treat EGFR mutated tumors. The trouble with KRAS is the insensitivity of upstream EGFR inhibition and the continuation of pathway signaling of BRAF/MEK/ERK leading to uncontrollable proliferation of the tumor cells. This literature review provides an overview of how KRAS is detected, how it effects downstream pathways and the future possibilities for treatment and more sensitive methodologies.