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Review
. 2020 Mar;146(3):631-645.
doi: 10.1007/s00432-020-03129-6. Epub 2020 Feb 17.

New advances in antiangiogenic combination therapeutic strategies for advanced non-small cell lung cancer

Huiping Qiang  1 , Qing Chang  1 , Jianlin Xu  1 , Jialin Qian  1 , Yanwei Zhang  1 , Yuqiong Lei  1 , Baohui Han  2 , Tianqing Chu  3
Affiliations
Review

New advances in antiangiogenic combination therapeutic strategies for advanced non-small cell lung cancer

Huiping Qiang et al. J Cancer Res Clin Oncol. 2020 Mar.

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.

Keywords: Anti-angiogenesis; Chemotherapy; Immunotherapy; NSCLC; Targeted therapy.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig.1
Fig.1
Dual inhibition of EGFR and VEGF signaling pathways could improve the antitumor effects (Tabernero 2007). EGFR epidermal growth factor receptor, VEGF vascular endothelial growth factor, bFGF basic fibroblast growth factor, TGF-α transforming growth factor-A, IL-8 interleukin-8, PIGF placenta growth factor
Fig. 2
Fig. 2
Combined inhibition of tumor angiogenesis and the immune checkpoint (Manegold et al. 2017). Arg1 arginase1, CD4 cluster of differentiation 4, CD8 cluster of differentiation 8, iDC immature dendritic cell, IDO indole amine 2, 3-dioxygenase, IL-10 interleukin-10, iNOS inducible nitric oxide synthase, MDSC myeloid-derived suppressor cell, NK natural killer, PD-L1 programmed death ligand 1, PGE2 prostaglandin E2, TAM Tyro3 Axl and Mer, R-NOS reactive nitrogen oxide species, TGFβ transforming growth factor β, Treg T-regulatory cell, VEGF vascular endothelial growth factor
See this image and copyright information in PMC

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