Nephrotoxicity of Anti-Angiogenic Therapies
Abstract
:1. Introduction
2. VEGF, Pro-Angiogenic Factor, Renal Expression
3. Anti-Angiogenic Drugs
3.1. Anti-VEGF mAb and Tyrosine Kinase Inhibitors
3.2. Other VEGF Signaling Inhibitors
3.2.1. RAF/MAPK/ERK Pathway
3.2.2. eNOS Pathway
3.2.3. mTOR Pathway
3.3. Current and Future Anti-Angiogenic Therapies
4. Adverse Effects of Anti-Angiogenic Therapy
4.1. Hypertension
4.2. Proteinuria
4.3. Kidney Dysfunction
4.4. Electrolyte Disorders
4.5. Cell Damages
4.5.1. Cytoskeleton and Focal Adhesion Architecture
4.5.2. Tubular Cell Apoptosis
4.5.3. Autophagy and mTOR Signaling
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Drugs | Molecular Targets | Tumor Targets | Adverse Events (Incidence) | Electrolytic Disorders | References |
---|---|---|---|---|---|
Monoclonal antibodies | |||||
Bevacizumab | VEGF | CRC, NSCLC, RCC, GBM, epithelial ovarian cancer, primary peritoneal cancer, cervical cancer, fallopian cancer, glioblastoma, ocular diseases | HTN (23–41%), Proteinuria (2–32%) | Hypophosphatemia, Hyponatremia | [38,39,40,41,42,43,44,45,46,47,48] |
Ranibizumab | VEGF | Ocular diseases | HTN, Proteinuria | - | [38,39] |
Ramucirumab | VEGFR2 | CRC, NSCLC, GC | HTN, Proteinuria | - | [38,39] |
Recombinant fusion protein | |||||
Aflibercept | VEGF | CRC, ocular diseases | HTN, Proteinuria | - | [38,39] |
Multitargeted TKI | |||||
Sorafenib | VEGFRs, PDGFRs, RAF, c-Kit, FLT3, Ret | RCC, HCC, DTC | HTN (17–55%), Proteinuria (10%) | Hypophosphataemia (16–85%), Hyponatremia (39%) | [49,50,51,52,53,54,55,56,57,58] |
Sunitinib | VEGFRs, PDGFRs, FLT3, CSF1R, Ret | RCC, GIST, pNETs | HTN (22–60%), Proteinuria (10–65%) | Hypophosphatemia, Hyponatremia | [59,60,61,62,63,64,65,66] |
Pazopanib | VEGFRs, PDGFRs, FGFR1, c-Kit | RCC, STS | HTN (40–52%), Proteinuria (13.5–18%) | Hypophosphatemia (34%), Hypocalcemia (33%), Hyponatremia (31%), Hypomagnesemia (11%) | [49,50,67,68,69,70,71,72,73] |
Vandetanib | VEGFRs, EGFR, Ret | MTC | HTN (23.5–84%), Proteinuria (5.6–26%) | Hypomagnesemia (10–40%)Hypocalcemia (4–29%)Hypokaliemia (4–17%) | [5,50,74,75,76,77,78,79] |
Axitinib | VEGFRs, PDGFRs, c-Kit | RCC | HTN (40–64%), Proteinuria (4.6–23%) | Hyponatremia, Hypophosphatemia (13%), Hypocalcemia (39%) | [5,49,50,80,81,82,83] |
Regorafenib | VEGFRs, PDGFRs, FGFRs, Tie2, c-Kit, Ret, RAF | GIST, CRC, HCC | HTN (13–59%), Proteinuria (7–9.4%) | Hypophosphataemia (5–18%) | [5,49,50,55,84,85,86] |
Cabozantib | VEGFRs, c-Met, AXL, c-Kit, FLT3, Ret | MTC, RCC | HTN (7–16), Proteinuria (6%) | Hypophosphatemia (4–8%) | [5,87,88,89,90,91] |
Nintedanib | VEGFRs, PDGFRs, FGFRs, SRC | IPF, NSCLC | HTN, Proteinuria | - | [92] |
Lenvatinib | VEGFRs, FGFRs, PDGFRa, Ret, c-Kit | DTC, RCC, HCC | HTN (45–100%), Proteinuria (26.9–100%) | Hypophosphatemia (45%) | [5,55,93] |
Dasatinib | BCR-ABL, SRC, LCK, YES, FYN, c-Kit, VEGFR, PDGFR | CML, Ph+ ALL | Proteinuria | Hyponatremia | [94,95] |
Ponatinib | VEGFRs, BCR-ABL, FLT3, Ret, c-Kit, FGFRs, PDGFR | CML, Ph+ ALL | HTN (9–32%) | - | [96,97,98] |
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Van Wynsberghe, M.; Flejeo, J.; Sakhi, H.; Ollero, M.; Sahali, D.; Izzedine, H.; Henique, C. Nephrotoxicity of Anti-Angiogenic Therapies. Diagnostics 2021, 11, 640. https://doi.org/10.3390/diagnostics11040640
Van Wynsberghe M, Flejeo J, Sakhi H, Ollero M, Sahali D, Izzedine H, Henique C. Nephrotoxicity of Anti-Angiogenic Therapies. Diagnostics. 2021; 11(4):640. https://doi.org/10.3390/diagnostics11040640
Chicago/Turabian StyleVan Wynsberghe, Margaux, Joanne Flejeo, Hamza Sakhi, Mario Ollero, Dil Sahali, Hassan Izzedine, and Carole Henique. 2021. "Nephrotoxicity of Anti-Angiogenic Therapies" Diagnostics 11, no. 4: 640. https://doi.org/10.3390/diagnostics11040640