Immune system molecule promotes tumor resistance to anti-angiogenic therapy

A team of scientists, led by Napoleone Ferrara, MD, has shown for the first time that a signaling protein involved in inflammation also promotes tumor resistance to anti-angiogenic therapy.

The findings by Ferrara – professor of pathology at the University of California, San Diego School of Medicine and senior deputy director for basic science at the UC San Diego Moores Cancer Center – and colleagues at Genentech, a biotechnology firm based in South San Francisco, are published in the August 4 Advance Online Publication of the journal Nature Medicine.

Angiogenesis is a physiological process in which new blood vessels form from existing vessels. It is fundamental to early development and wound healing, but some exploit angiogenesis to promote and fuel a tumor's transition from a benign to a malignant state.

In the late 1980s, Ferrara led efforts to identify a key gene (VEGF) involved in angiogenesis and subsequent development of the first drugs to block VEGF-mediated growth in a variety of cancers, among them lung, kidney, brain and colorectal. Researchers discovered, however, that similar to other therapies, VEGF-targeting drugs may lose effectiveness as tumors develop resistance, allowing cancers to recur.

The latest research highlights the role of interleukin-17 or IL-17, one of a family of signaling molecules called cytokines that are involved in the body's immune response. Ferrara and colleagues discovered that IL-17 signaling in tumor-infiltrating T cells, part of the body's , encourages resistance to the VEGF-blockade in mouse models.

"Our work has the potential to have major translational and therapeutic relevance," said Ferrara. "By inhibiting the effects of IL-17 with or other blockers, we can potentially improve the clinical efficacy of VEGF-targeting drugs."

More information: Nature Medicine DOI: 10.1038/nm.3291

Related Stories

A culprit behind brain tumor resistance to therapy

Mar 05, 2012

Persistent protein expression may explain why tumors return after therapy in glioblastoma patients, according to a study published on March 5th in the Journal of Experimental Medicine.

Fatty acid metabolite shows promise against cancer in mice

Apr 02, 2013

A team of UC Davis scientists has found that a product resulting from a metabolized omega-3 fatty acid helps combat cancer by cutting off the supply of oxygen and nutrients that fuel tumor growth and spread of the disease.

Cholesterol sets off chaotic blood vessel growth

May 29, 2013

A study at the University of California, San Diego School of Medicine identified a protein that is responsible for regulating blood vessel growth by mediating the efficient removal of cholesterol from the ...

Protein responsible for 'bad' blood vessel growth discovered

Jul 17, 2013

The discovery of a protein that encourages blood vessel growth, and especially 'bad' blood vessels – the kind that characterise diseases as diverse as cancer, age-related macular degeneration and rheumatoid arthritis – ...

Recommended for you

Clearing cells to prevent cervical cancer

4 hours ago

A study published online in the International Journal of Cancer earlier this month describes a novel approach to preventing cervical cancer based on findings showing successful reduction in the risk of cervical cancer after ...

Is Europe putting cancer research at risk?

7 hours ago

The European Society for Medical Oncology (ESMO), the leading pan-European association representing medical oncology professionals, has expressed concern that the proposed EU General Data Protection Regulation could make ...

User comments