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Updated: Jun 22, 2026

Investigating Angiogenesis on a Functional and Molecular Level by Leveraging the Scratch Wound Migration Assay and the Spheroid Sprouting Assay
Published on: May 31, 2024
Branching morphogenesis and antiangiogenesis candidates: tip cells lead the way
Peter Carmeliet1, Frederik De Smet, Sonja Loges
1Vesalius Research Center, VIB, KULeuven, Campus Gasthuisberg, Herestraat 49, Leuven, Belgium. peter.carmeliet@med.kuleuven.be
Abstract:
From the original concepts that tumors require a vascular supply to grow and that blocking angiogenesis could suppress tumor growth, the oncology field has witnessed clinical successes of VEGF-targeted antiangiogenic medicine. The field is now facing the challenge of overcoming resistance to VEGF-targeted therapy, and therefore additional angiogenesis inhibitors are being developed. Studies on how endothelial 'tip, stalk and phalanx cells' form sprouts have identified promising candidate targets with complementary mechanisms to VEGF. This Review provides a conceptual framework in which molecular discoveries and principles are discussed in light of clinical opportunities to develop new antiangiogenic agents.
Insights
Targeting tumor angiogenesis, particularly vascular endothelial growth factor (VEGF), has shown success. New angiogenesis inhibitors are being developed to overcome therapy resistance by targeting endothelial cell behaviors.
Area of Science:
- Oncology
- Cancer Biology
- Molecular Medicine
Background:
- Tumor growth depends on angiogenesis (new blood vessel formation).
- Vascular Endothelial Growth Factor (VEGF)-targeted therapies have achieved clinical success in oncology.
- Resistance to VEGF-targeted antiangiogenic therapy is a significant clinical challenge.
Purpose of the Study:
- To provide a conceptual framework for developing novel antiangiogenic agents.
- To discuss molecular discoveries and principles relevant to clinical antiangiogenesis strategies.
- To identify new therapeutic targets beyond VEGF for cancer treatment.
Main Methods:
- Review of molecular discoveries related to endothelial cell behavior in angiogenesis.
- Analysis of endothelial 'tip, stalk, and phalanx' cell functions.
- Integration of basic science findings with clinical opportunities.
Main Results:
- Identification of endothelial cell behaviors as promising targets for complementary antiangiogenic mechanisms.
- Understanding of how endothelial tip, stalk, and phalanx cells contribute to sprout formation.
- Framework for developing next-generation antiangiogenic drugs.
Conclusions:
- New antiangiogenic agents targeting endothelial cell dynamics offer potential to overcome VEGF-inhibitor resistance.
- A deeper understanding of angiogenesis mechanisms can guide the development of more effective cancer therapies.
- Clinical translation of novel molecular targets is crucial for advancing antiangiogenic medicine.
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