Massague: "We Have Discovered The First Genes Intervening In Brain Metastasis"

Main Category: Neurology / Neuroscience
Also Included In: Cancer / Oncology;  Genetics
Article Date: 18 Jun 2009 - 3:00 PDT

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Joan Massagué (Barcelona, Spain, 1953) is the first winner of the BBVA Foundation Frontiers of Knowledge Awards in the Biomedicine category. The Frontiers of Knowledge Awards are intended to recognize and promote research of excellence. The breadth of disciplines addressed and their monetary amount a combined purse of 3.2 million euros spread over eight prize categories place them among the world's foremost award schemes.

Massagué is Spain's most widely cited working scientist, with his papers referred to on more than 62,000 occasions. His studies, with great potential for clinical application, are opening up fundamental new pathways in the fight against cancer. He has conducted pioneering research into the genetic and cellular bases of metastasis and remains an acknowledged leader in this field.

His group's latest findings, published in the May edition of Nature, explain how tumor cells manage to enter the brain and form a new tumor. Until now, scientists were baffled as to how cancer cells were able to breach the blood-brain barrier which normally protects the brain from harmful substances. Massagué has identified three genes that intervene in the process, but the list will go on and work will continue to determine which is most important in each type of cancer.

Research into the genes involved in cerebral metastasis and their mode of action, "is still very much at the preliminary stage", says Massagué. "These are the first brain metastasis genes to be identified, with clinical data".

Dr. Massague's team is engaged in other research to ascertain how breast cancer cells survive from the time they leave the primary tumor and infiltrate vital organs to the time when, years later, they start to grow uncontrollably and form macrometastases. In the view of the Frontiers laureate, it is during these latent years that metastasis cells may be most vulnerable.

The focus of this research was breast cancer. And his team are now investigating whether the same genes may intervene in metastasis to other organs and in other types of cancer. In fact two have been verified in earlier studies as participating in breast cancer metastasis to the lungs.

Precisely another of Massague's major projects focuses on lung cancer metastasis, one of the biggest causes of cancer death. So far, his team has discovered the mechanisms whereby lung tumors invade the bones and the brain.

Aside from the above work, conducted at the Memorial Sloan-Kettering Cancer Center in New York, Massagué is collaborating on various projects on breast and bowel cancer, led by Roger Gomis and Eduard Batlle, at the IRB (Institute for Biomedical Research) in Barcelona. Their focus is on how metastases develop, with potential application further ahead in new drug development or by clinical research teams.

"The golden age of cancer research"

Research into metastasis is all-important, since this process whereby a tumor colonizes other organs is responsible for 90% of cancer-related deaths. So what is the current state of knowledge in this area? "We are just starting to explore the dark forest that is metastasis. But my group and others have begun to cut a path, and there are reasons to believe that we will shortly have an accurate map".

But his optimism is tinged with caution: "We have entered the golden era of cancer research, when we stand a good chance of understanding the genetic and environmental causes of this disease and improving its prevention and treatment," Massagué affirms. "Yet we must humbly recognize that this fight will take decades to produce an acceptable victory".

Each research advance opens new avenues for obtaining more effective pharmaceutical therapies. Joan Massagué's program, for instance, combines basic science with "translational" research, to ensure that the knowledge gained in the laboratory works through as quickly as possible to clinical practice. Massagué has this to say about the applied side of his work: "More than ever science permeates our everyday life. Biomedicine, at least, is a subject of great public interest and growing public understanding. Scientists respond to this demand by looking for faster ways to translate basic discoveries into practical knowledge with the power to solve health problems."

Hence the succinct phrase the scientist employs to express his research motivation: "To uncover the unknown for the service of mankind".

Massagué has over 340 publications to his name in leading scientific journals. He heads the Cancer Biology and Genetics Program at the Sloan-Kettering Institute, where he has pursued most of his scientific career. He is also a researcher at the Howard Hughes Medical Institute and adjunct director of the Institute for Biomedical Research (IRB Barcelona). His professional life, in other words, is a constant "shuttling between New York and Barcelona".

Among the milestones in his scientific career was the isolating of TGF-ß (transforming growth factor beta), a group of molecules segregated by tumor cells that make normal cells behave like cancer cells. We now know that TGF-ß is the principle inhibitor of cell growth. It is essential for the organism's normal development but, when disrupted, is also implicated in disease processes such as malformations and cancer. Massagué and his group identified the molecular pathway conveying the TGF-ß signal from the cell membrane to the nucleus rather like decoding the language it uses to communicate with other molecules and in this way have helped to elucidate one of the fundamental processes controlling cell division.

Award presentation ceremony

The presentation ceremony will take place on June 18 in the BBVA Foundation's Madrid headquarters under the presidency of the Minister of Science and Innovation, Cristina Garmendia, and the BBVA Foundation President, Francisco González. The event will welcome eminent members of the international scientific community and high-level government institutions alongside personalities from the worlds of business and the arts.

The Foundation is partnered in these awards by the Spanish National Research Council (CSIC), whose advisory input was instrumental in the appointment of the prize juries. The jury in the Biomedicine category was formed by Torsten Wiesel, Nobel Prize in Medicine; Angelika Schnieke, of the Technical University of Munich (Germany); Bruce Whitelaw, an expert in transgenic animals from the Roslin Institute (United Kingdom); Dario Alessi, of the Scottish Institute for Cell Signalling (United Kingdom); Robin Lovell-Badge, of the National Institute for Medical Research (United Kingdom); Josep Baselga, oncologist in the Hospital Vall d'Hebron Research Institute in Barcelona; and Juan Modolell of the Severo Ochoa Molecular Biology Center in Madrid, holder of the Santiago Ramón y Cajal Research Prize in Biology.

The BBVA Foundation supports knowledge generation, scientific research and the promotion of culture, relaying the results of its work to society at large. This effort materializes in research projects, human capital investment, specialization courses, grants and awards. Among the Foundation's preferred areas of activity are basic sciences, biomedicine, ecology and conservation biology, the social sciences and literary and musical creation.

Source: BBVA Foundation