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Published on: September 12, 2019
VEGF-targeted cancer therapeutics-paradoxical effects in endocrine organs
1Department of Microbiology, Tumour and Cell Biology, Karolinska Institutet, Nobels vag 16, 17177 Stockholm, Sweden.
Abstract:
Systemic administration of antiangiogenic drugs that target components of the vascular endothelial growth factor A (VEGF-A; VEGF) signal transduction pathway has become a viable therapeutic option for patients with various types of cancer. Nevertheless, these drugs can drive alterations in healthy vasculatures, which in turn are associated with adverse effects in healthy tissues. VEGF is crucial for vascular homeostasis and the maintenance of vascular integrity and architecture in endocrine organs. Given these critical physiological functions, systemic delivery of drugs that target VEGF signalling can block VEGF-mediated vascular functions in endocrine organs, such as the thyroid gland, and lead to endocrine dysfunction, including hypothyroidism, adrenal insufficiency and altered insulin sensitivity. This Review discusses emerging evidence from preclinical and clinical studies that contributes to understanding the mechanisms that underlie the vascular changes and subsequent modulations of endocrine function that are induced by targeted inhibition of VEGF signalling. Understanding these mechanisms is crucial for the design of antiangiogenic drugs with minimal associated adverse effects that will enable effective treatment of patients with cancer.
Insights
Antiangiogenic drugs targeting vascular endothelial growth factor A (VEGF-A) can cause endocrine dysfunction by affecting healthy blood vessels. Understanding these mechanisms is key to developing safer cancer therapies.
Area of Science:
- Endocrinology
- Oncology
- Vascular Biology
Background:
- Antiangiogenic drugs targeting vascular endothelial growth factor A (VEGF-A) are used in cancer therapy.
- These drugs can cause adverse effects in healthy tissues by altering vasculature.
- VEGF is vital for vascular homeostasis and integrity in endocrine organs.
Purpose of the Study:
- To review evidence on mechanisms linking VEGF signaling inhibition to endocrine dysfunction.
- To understand vascular changes induced by antiangiogenic drugs in endocrine glands.
- To inform the development of antiangiogenic therapies with reduced side effects.
Main Methods:
- Review of preclinical and clinical studies.
- Analysis of mechanisms underlying VEGF-targeted therapy side effects.
- Examination of effects on thyroid, adrenal, and insulin sensitivity.
Main Results:
- Targeted VEGF inhibition disrupts vascular homeostasis in endocrine organs.
- This disruption leads to endocrine dysfunctions like hypothyroidism and adrenal insufficiency.
- Altered insulin sensitivity is also a noted adverse effect.
Conclusions:
- Understanding VEGF-mediated vascular effects is crucial for cancer treatment.
- Developing antiangiogenic drugs with minimal endocrine adverse effects is a priority.
- This knowledge will improve patient outcomes in cancer therapy.
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