Public Release: 

Novel insights in MET-proto-oncogene might lead to optimizing cancer treatment

MET inhibitors could have a double-edged effect on tumors

VIB (the Flanders Institute for Biotechnology)

The MET-proto-oncogene is involved in the pathogenesis of several tumors and therefore represents an interesting target for future therapies currently tested in dozens of clinical trials. Veronica Finisguerra, Andrea Casazza, Max Mazzone and colleagues from VIB, KU Leuven and UZ Leuven now reveal that MET is needed for the recruitment of anti-tumoral neutrophils and puts a mechanism into action that promotes the killing of cancer cells. This means that the efficacy of a cancer therapy targeting MET in cancer cells will partly be countered by the pro-tumoral effect arising from MET blockade in neutrophils. These insights can lead to an optimization of the currently tested therapies based on MET-inhibitors and were published in the authorative journal Nature.

Max Mazzone (VIB/KU Leuven): "These findings are very important, because it affects a drug that is currently in clinical trials in which more than 15 companies are involved. Our results may be used to improve the efficacy of more than 20 drugs in preclinical trials and in phase I to phase III clinical trials based on patient stratification. Our work identifies an unprecedented role of MET in neutrophils and suggests a potential "Achilles' heel" of MET-targeted therapies in cancer."

MET in tumor immunity

Little was known about MET expression and function in tumor immunity. But this function is important because immune cells can restrain the growth and spread of malignant cells but can also foster tumor development and metastasis. The researchers have demonstrated that MET is induced by TNF-α during pathophysiological inflammation such as skin rash, peritonitis and cancer. MET is then required for HGF-dependent neutrophil migration through the vessel wall of inflamed tissues where neutrophils exert anti-microbial and anti-tumoral functions.

From an immunological point of view, this highlights a clever and fine control of non-specific immune reactions, which is necessary in order to prevent damage to healthy organs and, conversely to confine this cytotoxic response to the site of inflammation.

A double-edged effect

From a therapeutic point of view, it indicates that MET inhibitors could have a double-edged effect on tumors: on the one hand, acting on cancer cells that rely on MET hyperactivation for growth and survival, MET inhibitors would encourage cell-cycle arrest or cell death; on the other hand, acting on neutrophils, they would crucially blunt pro-inflammatory, anti-tumorigenic reactions.

Max Mazzone (VIB/KU Leuven): "This work indicates that patients should be enrolled in clinical trials with anti-MET drugs based on MET expression and dependency of the cancer cell itself, excluding those patients that have high MET expression in the immune infiltrate."

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Relevant publication

The above-mentioned research was published in Nature (Finisguerra et al., Nature 2015).

Questions

Given that this research can raise many questions, we would like to refer your questions in your report or article to the email address that the VIB has made available for this purpose. All questions regarding this and other medical research can be directed to: patients@vib.be.

Note to the editor

*** EMBARGO: 18 May 1600 London time ***

Learn more about the work of Max Mazzone by attending the VIB conference 'Metabolism in Cancer and Stromal Cells' that will take place from 8-10 September in Leuven, Belgium.

During this international meeting 19 renowned researchers will focus on how cancer and stromal cells metabolically communicate and how their specific metabolism impacts disease development and progression. These insights into cellular metabolism also offer novel therapeutic opportunities for malignant, metabolic, or inflammatory disease.

More info via http://www.vibconferences.be

Credits

When reporting on this research, please mention all partners involved.

VIB

VIB is a non-profit research institute in life sciences. About 1,400 scientists conduct strategic basic research on the molecular mechanisms that are responsible for the functioning of the human body, plants, and microorganisms. Through a close partnership with four Flemish universities ? UGent, KU Leuven, University of Antwerp, and Vrije Universiteit Brussel ? and a solid funding program, VIB unites the forces of 74 research groups in a single institute. The goal of the research is to extend the boundaries of our knowledge of life. Through its technology transfer activities, VIB translates research results into products for the benefit of consumers and patients and contributes to new economic activity. VIB develops and disseminates a wide range of scientifically substantiated information about all aspects of biotechnology. More information: http://www.vib.be.

KU Leuven

KU Leuven (University of Leuven) is a leading European research university dedicated to excellent research, education and service to society. It is a founding member of the League of European Research Universities and has a strong European and international orientation. Its sizeable academic staff conducts basic and applied research in a comprehensive range of disciplines. University Hospitals Leuven, its network of research hospitals, provides high-quality healthcare and develops new therapeutic and diagnostic insights with an emphasis on translational research. The university welcomes more than 40,000 students, of which 15.5% are international from more than 140 countries. Its doctoral schools organise internationally oriented PhD programmes for over 4,000 doctoral students. http://www.kuleuven.be/english/

Contact

Massimiliano Mazzone - VIB scientist - +32 485 40 49 04
Massimiliano.mazzone@vib-kuleuven.be

Sooike Stoops - Science Communications Expert- +32 474 289 252
sooike.stoops@vib.be

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