Tumor Neovascularization and Developments in Therapeutics
Abstract
:1. Introduction
2. Molecules Involved in Neovascularization
3. Characteristics of Angiogenic Tumor Vessels
4. Regulatory Mechanisms of Neovascularization
4.1. HIF-1α
4.2. Endoplasmic Reticulum Stress Signals
5. Antiangiogenic Therapy
6. Resistance Mechanism of Angiogenesis Inhibitors
7. Neovascularization and Immunity
8. Angiogenesis Inhibitors and Immunotherapy
9. Conclusions
Author Contributions
Acknowledgments
Conflicts of Interest
References
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Activators | Functions | Inhibitors | Functions |
---|---|---|---|
Vascular endothelial growth factor family | Induction of angiogenesis, enhancement of vascular permeability | Angiopoietin-2 | Antagonist of Ang1 |
Epidermal growth factor | Promotes growth of vascular endothelial cells | Thrombospondin-1,2 | Inhibits endothelial migration, growth, adhesion and survival |
Fibroblast growth factor | Induction of angiogenesis | collagen | Substrate for MMPs |
Platelet-derived growth factor | Involved in migration of vascular endothelial cells | Endostatin | Inhibits endothelial survival and migration |
Angiopoietin-1 | Stabilization of vascular endothelium | Angiostatin | Suppresses tumor angiogenesis |
Transforming growth factor | Production of extracellular matrix | TIMPs | Suppresses pathological angiogenesis |
Ephrin | Control of blood vessel and lymph duct formation | Platelet Factor-4 | Inhibits binding of bFGF and VEGF |
Matrix metalloproteinase | Degradation of extracellular matrix, activation of angiogenesis inducing factor | Vasostatin | Inhibits endothelial growth |
Drug | Target Molecule | Approved Disease |
---|---|---|
Bevacizumab | Anti-VEGF monoclonal antibody | mCRC, NSCLC, mRCC, ovarian cancer, malignant glioma, advanced cervical cancer, fallopian tube cancer, primary peritoneal cancer |
Ramucirumab | Anti-VEGFR2 monoclonal antibody | Advanced gastric or gastroesophageal junction adenocarcinoma, NSCLC, advanced colorectal cancer |
Ziv-aflibercept | Soluble decoy of VEGFR | Metastatic colorectal cancer |
Sunitinib | TKI: VEGFR, PDGFR, FLT3, KIT | RCC, Gastrointestinal stromal tumor, pancreatic neuroendocrine tumor |
Sorafenib | TKI: VEGFR, PDGFR, FLT3, KIT, Raf | RCC, unresectable hepatocellular carcinoma, metastatic or recurrent thyroid carcinoma |
Axitinib | TKI: VEGFR, PDGFR, KIT | Advanced RCC |
Pazopanib | Multiple targeted receptor TKI | RCC, Advanced soft tissue sarcoma |
Vandetanib | TKI: VEGFR, EGFR, RET | Unresectable or metastatic medullary thyroid cancer |
Tumor Type | Combination Drugs | Study Status | NCT ID |
---|---|---|---|
Stage IV NSCLC | Atezolizumab+Carboplatin+paclitaxel+Bevacizumab | Active, not recruiting | NCT02366143 |
Advanced RCC | Bevacizumab+Atezolizumab | Active, not recruiting | NCT02420821 |
Advanced RCC | Avelumab+Axitinib | Active, not recruiting | NCT02684006 |
Advanced RCC | Lenvatinib/Everolimus or Lenvatinib/Pembrolizumab | Recruiting | NCT02811861 |
Recurrent OC, FTC, or PPC | Pegylated Liposomal Doxorubicin+Atezolizumab+Bevacizumab | Recruiting | NCT02839707 |
RCC | Pembrolizumab+Axitinib | Active, not recruiting | NCT02853331 |
Late relapse OC | Atezolizumab+Chemotherapy+Bevacizumab | Recruiting | NCT02891824 |
OC,FTC,or PPC | Atezolizumab+Carboplatin+paclitaxel+Bevacizumab | Recruiting | NCT03038100 |
Early relapse OC | Atezolizumab+Bevacizumab+Chemotherapy | Recruiting | NCT03353831 |
Locally Advanced or Metasatatic HCC | Atezolizumab+Bevacizumab | Recruiting | NCT03434379 |
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Katayama, Y.; Uchino, J.; Chihara, Y.; Tamiya, N.; Kaneko, Y.; Yamada, T.; Takayama, K. Tumor Neovascularization and Developments in Therapeutics. Cancers 2019, 11, 316. https://doi.org/10.3390/cancers11030316
Katayama Y, Uchino J, Chihara Y, Tamiya N, Kaneko Y, Yamada T, Takayama K. Tumor Neovascularization and Developments in Therapeutics. Cancers. 2019; 11(3):316. https://doi.org/10.3390/cancers11030316
Chicago/Turabian StyleKatayama, Yuki, Junji Uchino, Yusuke Chihara, Nobuyo Tamiya, Yoshiko Kaneko, Tadaaki Yamada, and Koichi Takayama. 2019. "Tumor Neovascularization and Developments in Therapeutics" Cancers 11, no. 3: 316. https://doi.org/10.3390/cancers11030316