Nowadays, the cornerstone status of chemotherapy in advanced non-small cell lung cancer (NSCLC) is seriously challenged and its therapeutic effect has hit the bottlenecks. With the combination of chemotherapy and molecular targeted drugs, antiangiogenic agents or immunotherapy drugs, tapping the potential of chemotherapeutic drugs and developing new chemotherapeutic drugs, searching the biomarkers that can predict the efficacy of chemotherapy, most patients with advanced NSCLC may get the maximum benefit from chemotherapy.
Last decade, EGFR-TKI have led the way of precision medicine for NSCLC and have made significant breakthroughs in the treatment of advanced NSCLC. The treatment concept of NSCLC have changed from traditional chemoradiotherapy based on pathological type to precise treatment based on molecular type. Optimizing the management of the third generation of EGFR-TKI, expanding the indications of EGFR-TKI, improving efficacy with the combination of other treatments, exploring the mechanisms and strategies of drug resistance are significant challenges for EGFR-TKI.
Immunotherapy acts as one of developing therapeutic strategies following traditional surgery, radiation therapy and chemotherapy. Recently, immunotherapy shows increasing importance in the comprehensive treatment of advanced non-small cell lung cancer (NSCLC) because of its significant relaibility and efficacy. Several programmed cell death protein 1/ programmed death ligand 1 (PD-1/PD-L1) inhibitors have been approved for the treatment of advanced or metastatic NCCLC in first or second-line setting. In addition, immunotherapy with PD-L1 inhibitor promotes progression-free survival in stage III NSCLC patients who received previously concurrent radiation therapy and chemotherapy. However, due to the limited number of patients who could benefit from approved immunotherapy and the aim of expanding benifit groups, the immunotherapy treatment model of advanced NSCLC still needs continuous optimization, which includes immunotherapy combined with chemotherapy or immunotherapy combined with radiation therapy . Tumor marker-based precision therapy and efficacy with immunotherapy are in rapid development and improvement.
Tumor neovascularization is the basis of tumor growth, progression and metastasis, involving various cell-mediated signal transduction pathways, and many factors that promote / inhibit angiogenesis. Among them, the strongest growth factor that stimulates angiogenesis is vascular endothelial growth factor(VEGF), which acts by binding to the vascular endothelial growth factor receptor (VEGFR). VEGF / VEGFR pathway inhibitors are now widely used in clinical treatment, a new generation of anti-tumor angiogenesis drug research and development has also made some breakthrough. This article reviews the mechanism of tumor angiogenesis, different molecules pathways of anti-tumor angiogenesis drugs and drug resistance mechanisms in the treatment of non-small cell lung cancer.