Advances in Molecular Biology of Lung Disease: Aiming for Precision Therapy in Non-small Cell Lung Cancer

摘要

In the past few years, increasingly refined methods of tissue sampling in combination with new insights in molecular biology have swiftly altered the diagnostic and therapeutic landscape of non-small cell lung cancer (NSCLC), allowing us the opportunity to develop treatments for a subset of molecularly well-defined patients. Large-scale genomic, mutational, and proteomic profiling studies of NSCLC have succeeded in identifying the presence of mutually exclusive driver mutations throughout the full gamut of NSCLC histology and smoker status. For example, in approximately 60% of lung adenocarcinomas, mutations in multiple oncogenes are readily apparent, including protein kinase B-α (AKT1), anaplastic lymphoma kinase (ALK), protein kinase B-raf (BRAF), epidermal growth factor receptor (EGFR), human epidermal growth factor receptor (HER) 2, Kirsten rat sarcoma viral oncogene homolog (KRAS), dual-specificity mitogen-activated protein kinase kinase (MEK) 1, hepatocyte growth factor receptor (MET), NRAS (neuroblastoma RAS viral oncogene homolog), phosphoinositide-3-kinase catalytic α-polypeptide (PI3KCA), “rearranged during transfection” protooncogene (RET), and protooncogene receptor tyrosine kinase (ROS1). However, within this population, never smokers with adenocarcinoma are identified as having the highest likelihood of EGFR, HER2, ALK, RET, and ROS1 mutations.