Abstract
Purpose
Tumor growth relies on the sufficient blood supply and continuously requires new blood vessels to maintain, which lead to vascular abnormalities (Folkman, N Engl J Med 285:1182–1186, 1971). Antiangiogenic therapy has emerged with the goal of normalizing vasculature and tumor microenvironment (TME). Some antiangiogenic therapies combined with chemotherapy, targeted therapy or immunotherapy have been approved for clinical application. In this review, we summarize the recent advances of antiangiogenic combination therapeutic strategies in advanced NSCLC.
Methods
References of this review are searched through PubMed and EMBASE and the abstracts of cancer conferences. The ClinicalTrials.gov database was used for relative trials.
Results
Based on different mechanisms, antiangiogenic agents can be divided into monoclonal antibodies (mAbs), which mainly include bevacizumab and ramucirumab, and multi-target antiangiogenic tyrosine kinase inhibitors (TKIs) which include sunitinib, sorafenib, nintedanib, apatinib, anlotinib, fruquintinib, etc. In recent years, a number of large clinical studies have shown that antiangiogenic agents have conferred a significant overall survival (OS) benefit to patients with advanced non-small cell lung cancer (NSCLC). More and more evidences confirm that the combination of antiangiogenic agents with chemotherapy, targeted therapy and immunotherapy can improve the effect and prolong the survival of NSCLC patients. However, many problems about the application of antiangiogenic agents on advanced NSCLC patients still need to be explored. For example, the combination therapy of multi-target antiangiogenic agents is just beginning, and the biomarkers are not clear.
Conclusions
Antiangiogenic agents can achieve therapeutic benefit in advanced NSCLC patients and the combination of chemotherapy, targeted therapy or immunotherapy can lead to synergistic effect. However, exploring the best combination therapy and efficacy-related biomarkers needs further study.
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Abbreviations
- TME:
-
Tumor microenvironment
- mAbs:
-
Monoclonal antibodies
- TKIs:
-
Tyrosine kinase inhibitors
- OS:
-
Overall survival
- NSCLC:
-
Non-small cell lung cancer
- VEGF:
-
Vascular endothelial growth factor
- PDGF:
-
Platelet-derived growth factor
- FGF:
-
Fibroblast growth factor
- Ang:
-
Angiotensin
- HGF:
-
Hepatocyte growth factor
- EGF:
-
Epidermal growth factor
- VEGFR:
-
Vascular endothelial generated factor receptor
- FDA:
-
The Food and Drug Administration
- VEGF-A:
-
Vascular endothelial growth factor-A
- ORR:
-
Objective response rate
- PFS:
-
Progression-free survival
- EGFR:
-
Epidermal growth factor receptor
- LUAD:
-
Lung adenocarcinoma
- PDGFR:
-
Platelet-derived growth factor receptor
- FGFR:
-
Fibroblast growth factor receptor
- DCR:
-
Disease control rate
- CNS:
-
Central nervous system
- ALK:
-
Anaplastic lymphoma kinase
- KIT:
-
Stem-cell factor receptor
- FLT3:
-
FMS-like tyrosine kinase 3
- CSF1R:
-
Colony-stimulating factor 1 receptor
- RET:
-
Rearranged during transfection
- PD-1:
-
Programmed cell death protein 1
- PD-L1:
-
Programmed cell death protein ligand 1
- ICAM-1:
-
Endothelial cell adhesion molecule-1
- VCAM-1:
-
Vascular cell adhesion molecule-1
- Tregs:
-
Regulatory T cells
- DC:
-
Dendritic cells
- GM-CSF:
-
Granulocyte macrophage colony-stimulating factor
- ABCP:
-
Atezolizumab plus bevacizumab and paclitaxel/carboplatin
- BCP:
-
Bevacizumab plus paclitaxel/carboplatin
- G/GEJ:
-
Gastric or gastroesophageal junction
- UC:
-
Urothelial carcinoma
- TMB:
-
Tumor mutation burden
- MVD:
-
Micro-vessel density
- Teff:
-
Effector T cell
- CCL2:
-
Chemokine ligand 2
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This review is supported by the Western Medicine Guide Project of Shanghai Committee of Science and Technology (Grant nos. 16411964700 and 18411968500).
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Qiang, H., Chang, Q., Xu, J. et al. New advances in antiangiogenic combination therapeutic strategies for advanced non-small cell lung cancer. J Cancer Res Clin Oncol 146, 631–645 (2020). https://doi.org/10.1007/s00432-020-03129-6
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DOI: https://doi.org/10.1007/s00432-020-03129-6