Peptides as Anti-Angiogenic Agents

Anti-angiogenic peptides are an emerging class of cancer therapeutics that inhibit the formation of new blood vessels, angiogenesis, in tumors. By disrupting angiogenesis, these peptides starve the tumor of oxygen and nutrients, ultimately inhibiting tumor growth and metastasis. Angiogenesis is a critical process in cancer progression, and peptides that target angiogenic pathways offer a novel approach to controlling tumor growth.¹

Mechanism of Action

Anti-angiogenic peptides typically function by targeting key molecules involved in angiogenesis, such as vascular endothelial growth factor, VEGF, and its receptors. Peptides can inhibit the binding of VEGF to its receptor, preventing the activation of downstream signaling pathways that promote endothelial cell proliferation and migration. Some peptides, like thrombospondin-1-derived peptides, inhibit angiogenesis by promoting endothelial cell apoptosis.²

Therapeutic Applications

Anti-angiogenic peptides are being developed as therapies for various solid tumors, including colorectal cancer, lung cancer, and glioblastoma. For example, Cilengitide, a cyclic peptide targeting integrins, has been investigated for its ability to inhibit angiogenesis in glioblastoma.³ Additionally, peptides derived from endostatin and angiostatin are under investigation for their ability to inhibit tumor angiogenesis in preclinical and clinical settings.⁴

Challenges and Future Directions

Although anti-angiogenic peptides show great promise, challenges remain in improving their bioavailability and stability in vivo. Efforts to enhance peptide stability through chemical modifications, such as PEGylation, are ongoing. Additionally, researchers are exploring the use of combination therapies with anti-angiogenic peptides and immune checkpoint inhibitors to improve overall therapeutic outcomes.⁵.

Conclusion

Peptides as anti-angiogenic agents represent a promising avenue in cancer therapy, offering a targeted approach to inhibiting tumor growth. Ongoing research into peptide stability and combination therapies is likely to enhance their therapeutic potential in clinical settings.

Citations and Links

1. Folkman, Judah. “Role of Angiogenesis in Tumor Growth and Metastasis.” Seminars in Oncology, vol. 29, no. 6, 2002, pp. 15–18. doi:10.1016/S0093-7754(02)70100-1.

2. Sid B., et al. “Thrombospondin-1 and VEGF in Tumor Angiogenesis: Modulation by Anti-Angiogenic Peptides.” Peptides, vol. 30, no. 3, 2009, pp. 426–435. doi:10.1016/j.peptides.2008.11.013.

3. Nabors, Louis B., et al. “Cilengitide in Patients with Recurrent Glioblastoma Multiforme: Results of Phase II Open-Label Trial.” Journal of Clinical Oncology, vol. 27, no. 28, 2009, pp. 4743–4750. doi:10.1200/JCO.2009.22.5129.

4. O’Reilly, Michael S., et al. “Endostatin: An Endogenous Inhibitor of Angiogenesis and Tumor Growth.” Cell, vol. 88, no. 2, 1997, pp. 277–285. doi:10.1016/S0092-8674(00)81866-2.

5. Kerbel, Robert S. “Antiangiogenic Therapy: A Universal Chemosensitization Strategy for Cancer?” Science, vol. 312, no. 5777, 2006, pp. 1171–1175. doi:10.1126/science.1125950.