Abstract
Anti-angiogenic therapy has been demonstrated to increase progression-free survival in patients with many different solid cancers. Unfortunately, the benefit in overall survival is modest and the rapid emergence of drug resistance is a significant clinical problem. Over the last decade, several mechanisms have been identified to decipher the emergence of resistance. There is a multitude of changes within the tumor microenvironment (TME) in response to anti-angiogenic therapy that offers new therapeutic opportunities. In this review, we compile results from contemporary studies related to adaptive changes in the TME in the development of resistance to anti-angiogenic therapy. These include preclinical models of emerging resistance, dynamic changes in hypoxia signaling and stromal cells during treatment, and novel strategies to overcome resistance by targeting the TME.
Highlights
Angiogenesis is well recognized as an important step in the growth and progression of many tumor types[1]
Over the last 15 years, anti-angiogenic therapy has become an effective modality for cancer therapy
Several vascular endothelial growth factor/receptor (VEGF/R) inhibitors have been approved by the US Food and Drug Administration for various solid tumors, including metastatic colorectal cancer, metastatic renal cell cancer, metastatic gastric cancer, non-small-cell lung cancer, recurrent/metastatic cervical cancer, recurrent ovarian cancer, and glioblastoma multiforme (GBM)
Summary
Angiogenesis is well recognized as an important step in the growth and progression of many tumor types[1]. Cyclooxygenase-2; CSF1, colony-stimulating factor 1; CXCL, C-X-C chemokine ligand; CXCR, C-X-C chemokine receptor; EC, endothelial cell; EMT, epithelial-to-mesenchymal transition; EPC, endothelial progenitor cell; FAK, focal adhesion kinase; FGF, fibroblast growth factor; FGFR, fibroblast growth factor receptor; FIH-1, factor inhibiting 1; GBM, glioblastoma multiforme; HCC, hepatocellular carcinoma; HDAC, histone deacetylase; HIF, hypoxia-inducible factor; IL, interleukin; mCRC, metastatic colorectal cancer; MAPK, mitogen-activated protein kinase; MDSC, myeloid-derived suppressor cell; MIF, macrophage inhibitory factor; MMP, matrix metalloproteinase; MSC, mesenchymal stem cell; mTOR, mammalian target of rapamycin; NAC1, nucleus accumbens-associated protein-1; Nrp[1], neuropilin-1; OGDH, oxoglutarate dehydrogenase; OS, overall survival; PD-1, programmed cell death-1; PDGF, platelet-derived growth factor; PECAM, platelet endothelial cell adhesion molecule; PFS, progression-free survival; PHD, prolyl hydroxylase domain; ROS, reactive oxygen species; SA, saltern amide A; SDF1, stromal cell-derived factor 1; TAM, tumor-associated macrophage; TEC, tumor endothelial cell; TEM, Tie2-expressing macrophage; TGF-β, transforming growth factor-beta; TME, tumor microenvironment; VDA, vascular disrupting agent; VE-cadherin, vascular endothelial cadherin; VEGF/R, vascular endothelial growth factor/receptor; VM, vasculogenic mimicry
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
