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Lung metastases can evade therapy by ‘hijacking’ blood vessels of the lung

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(Vienna, 06-12-2016) A new international study which was a collaboration between research groups based in Austria (Medical University of Vienna), England, Belgium and Hungary shows that cancer which spreads to the lungs can hijack lung blood vessels in order to resist therapy.

Lung metastasis is a life-threatening stage of cancer that develops when cancer cells that originated in another part of the body (such as the breast, bowel or kidney) spread to the lungs. The formation of new blood vessels – angiogenesis – has been considered crucial for lung metastases to grow; and several drugs have been designed to target this new blood vessel growth in order to prevent tumor progression. However, these drugs designed to target the tumor vasculature in lung metastases (anti-angiogenic drugs) have often shown disappointing results in patients.

In the new study it was shown that, instead of inducing new blood vessel growth, many human lung metastases can recruit pre-existing blood vessels in the lung. Moreover, the study shows, for the first time, that the ability of lung metastases to recruit pre-existing blood vessels offers an important explanation as to why anti-angiogenic drugs have shown disappointing results in patients with lung metastasis.

This is an important step towards developing more efficient and personalized treatments for patients with lung metastases

In this international collaboration, the scientists involved analysed 164 lung metastasis samples from patients with breast, bowel and kidney cancer. The study found that, in over 80% of the cases examined, the lung metastases could use pre-existing lung vessels to fuel tumor growth instead of, or as well as, generating new blood vessels. The study required the expertise of thoracic surgeons, pathologists and biologists all working together.

Study co-leader Dr. Andrew Reynolds, Team Leader in Tumour Biology at the Breast Cancer Now Toby Robins Research Centre at The Institute of Cancer Research, London, said: “Our research helps to explain why drugs designed to inhibit angiogenesis have been relatively ineffective in the treatment of patients with lung metastases. These new findings suggest that rather than making their own blood vessels, lung metastases often co-opt pre-existing lung blood vessels instead. It also suggests that we should be exploring whether combination treatments – blocking both new blood vessel growth and vessel co-option – could be a more effective way of denying these cancers the vasculature they need.”

The study, which was recently published in The Journal of Pathology, provides a detailed description of three distinct mechanisms through which lung metastases incorporate pre-existing lung blood vessels. This new insight might ultimately lead to novel therapeutic approaches.

Study co-leader Balazs Dome, the Head of the Translational Thoracic Oncology Program at the Medical University of Vienna added: “The frequent occurrence of vessel co-option warrants that novel therapies should be developed that can target both neoangiogenesis and vessel co-option in order to efficiently interfere with metastatic tumor growth."

Whilst the study focused on tumors which spread to the lungs, the findings prompt further research into how cancers can recruit a blood supply when they spread to other parts of the body. In the long-term, future studies of this kind should lead to more efficient and personalized treatments for patients with cancer that has spread to other parts of the body.

The work was funded by leading UK charity Breast Cancer Now, with additional support from the Hungarian Scientific Research Fund, a Semmelweis University Start-Up grant, the ÖNB Jubiläumsfondsprojekt and the Vienna Fund for Innovative Interdisciplinary Cancer Research.

Publication: Bridgeman VL, Vermeulen PB, Foo S, Bilecz A, Daley F, Kostaras E, Nathan MR, Wan E, Frentzas S, Schweiger T, Hegedus B, Hoetzenecker K, Renyi-Vamos F, Kuczynski EA, Vasudev NS, Larkin J, Gore M, Dvorak HF, Paku S, Kerbel RS, Dome B, Reynolds AR. "Vessel co-option is common in human lung metastases and mediates resistance to anti-angiogenic therapy in preclinical lung metastasis models." J Pathol. http://onlinelibrary.wiley.com/doi/10.1002/path.4845/abstract
DOI: 10.1002/path.4845.