Targeted therapies for advanced non-small cell lung cancer

Abstract

Lung cancer is a serious health problem and the leading cause of cancer death worldwide, due to its high incidence and mortality. 85% of lung cancers are represented by the non-small cell lung cancer (NSCLC). Traditional chemotherapy has been the main treatment option in NSCLC. However, it is often associated with limited efficacy and overall poor patient survival. In recent years, molecular targeting has achieved great progress in therapeutic treatment of cancer and plays a crucial role in the current clinical treatment of NSCLC, due to enhanced efficacy on cancer tissues and reduced toxicity for normal tissues. In this review, we summarize the current targeting treatment of NSCLC, including inhibition of the epidermal growth factor receptor (EGFR), phosphatidylinositol 3-kinase (PI3Ks), mechanistic target of rapamycin (mTOR), epidermal growth factor receptor 2 (ErbB2), vascular epidermal growth factor receptor (VEGFR), kirsten human rat sarcoma protein (KRAS), mesenchymal-epithelial transition factor or hepatocyte growth factor receptor (c-MET), anaplastic lymphoma kinase (ALK), v-Raf murine sarcoma viral oncogene homolog B (BRAF). This article may serve as a guide to clinicians and researchers alike by assisting in making therapeutic decisions. Challenges of acquired drug resistance targeted therapy and imminent newer treatment modalities against NSCLC are also discussed.

Keywords: EGFR; NSCLC; PI3K; mTOR; molecular target.

Figure 1. Molecular targets in NSCLC

Various mechanisms including amplification and mutation may lead to activation of EGFR, PI3K, mTOR, HER2, KRAS, c-MET, ALK, BRAF and corresponding signaling pathways, while targeting inhibitors suppress the activation in NSCLC and result in therapeutic effects.

Figure 2. Occurrence of genetic changes in NSCLC

The frequency of different genetic changes occurred in NSCLC including EGFR, ALK, KRAS, HER2, BRAF, PI3KCA.