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Updated: Dec 7, 2025
Chemotherapy-induced Vascular Toxicity - Real-time In vivo Imaging of Vessel Impairment
Published on: January 7, 2015
Vascular toxicity associated with anti-angiogenic drugs
Karla B Neves1, Augusto C Montezano1, Ninian N Lang1
1Institute of Cardiovascular and Medical Sciences, University of Glasgow, U.K.
Abstract:
Over the past two decades, the treatment of cancer has been revolutionised by the highly successful introduction of novel molecular targeted therapies and immunotherapies, including small-molecule kinase inhibitors and monoclonal antibodies that target angiogenesis by inhibiting vascular endothelial growth factor (VEGF) signaling pathways. Despite their anti-angiogenic and anti-cancer benefits, the use of VEGF inhibitors (VEGFi) and other tyrosine kinase inhibitors (TKIs) has been hampered by potent vascular toxicities especially hypertension and thromboembolism. Molecular processes underlying VEGFi-induced vascular toxicities still remain unclear but inhibition of endothelial NO synthase (eNOS), reduced nitric oxide (NO) production, oxidative stress, activation of the endothelin system, and rarefaction have been implicated. However, the pathophysiological mechanisms still remain elusive and there is an urgent need to better understand exactly how anti-angiogenic drugs cause hypertension and other cardiovascular diseases (CVDs). This is especially important because VEGFi are increasingly being used in combination with other anti-cancer dugs, such as immunotherapies (immune checkpoint inhibitors (ICIs)), other TKIs, drugs that inhibit epigenetic processes (histone deacetylase (HDAC) inhibitor) and poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors, which may themselves induce cardiovascular injury. Here, we discuss vascular toxicities associated with TKIs, especially VEGFi, and provide an up-to-date overview on molecular mechanisms underlying VEGFi-induced vascular toxicity and cardiovascular sequelae. We also review the vascular effects of VEGFi when used in combination with other modern anti-cancer drugs.
Insights
Vascular endothelial growth factor inhibitors (VEGFi) and tyrosine kinase inhibitors (TKIs) revolutionize cancer treatment but cause hypertension and thromboembolism. Understanding VEGFi
Area of Science:
- Oncology and Pharmacology
- Cardiovascular Research
- Molecular Biology
Background:
- Cancer treatment has advanced with molecular targeted therapies and immunotherapies, including VEGF inhibitors (VEGFi) and tyrosine kinase inhibitors (TKIs).
- While effective, these therapies can cause significant vascular toxicities, notably hypertension and thromboembolism.
- The precise molecular mechanisms driving these VEGFi-induced vascular toxicities remain unclear, necessitating further investigation.
Purpose of the Study:
- To elucidate the molecular mechanisms underlying vascular toxicities induced by VEGF inhibitors (VEGFi).
- To review the cardiovascular sequelae associated with VEGFi and other tyrosine kinase inhibitors (TKIs).
- To examine the vascular effects of VEGFi when used in combination with other modern anti-cancer drugs, including immunotherapies.
Main Methods:
- Review of current literature on molecular targeted therapies and immunotherapies in cancer treatment.
- Analysis of implicated molecular pathways in VEGFi-induced vascular toxicity, such as nitric oxide synthase inhibition and oxidative stress.
- Examination of studies investigating combination therapies involving VEGFi and other anti-cancer agents.
Main Results:
- VEGF inhibitors (VEGFi) and tyrosine kinase inhibitors (TKIs) are associated with significant vascular toxicities, including hypertension and thromboembolism.
- Potential mechanisms include inhibition of endothelial nitric oxide synthase (eNOS), reduced nitric oxide (NO) production, oxidative stress, endothelin system activation, and vascular rarefaction.
- Combination therapies with immunotherapies and other agents may exacerbate cardiovascular risks.
Conclusions:
- There is an urgent need to understand the molecular basis of VEGFi-induced cardiovascular diseases (CVDs).
- VEGFi and TKIs, while crucial for cancer therapy, require careful monitoring for vascular adverse events.
- Further research into combination therapy effects is essential to mitigate cardiovascular risks in cancer patients.
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