Chair of the Cancer Biology and Genetics Program at the Memorial Sloan Kettering Cancer Center in New York (United States). Currently Director of the Sloan Kettering Institute (United States)
Joan Massagué i Solé (Barcelona, Spain; 1953), earned a PhD in Pharmacy and Biochemistry from the University of Barcelona in 1978. In 1982, he became Assistant Professor of Biochemistry at the University of Massachusetts Medical School (United States). In 1989, he took up the Alfred P. Sloan Chair in Cancer Biology at the Memorial Sloan Kettering Cancer Center, and was appointed a Howard Hughes Medical Institute investigator.
He served as Chairman of the Sloan Kettering Institute Cell Biology Program from 1989 to 2003 and has been a Founding Chair of the Cancer Biology and Genetics Program since 2003. In 2014, he was appointed Director of the Sloan Kettering Institute. He is also co-founder of IRB Barcelona and president of its External Advisory Board.
Massagué is a member of the American Academy of Arts and Sciences, the U.S. National Academy of Sciences and the same country’s Institute of Medicine, as well as of the Spanish Royal Academies of Medicine and of Pharmacy, the European Molecular Biology Organization and the Ibero-American Academy of Pharmacy. His distinctions include the Vilcek Prize (2006), the Passano Prize (2007), the Rey Juan Carlos I National Research Prize, the Santiago Ramón y Cajal National Research Prize in the Biology area (2014) and the Premi Internacional Catalunya (2016).
Speech
Biomedicine, 1st edition
What is it that drives a tumor cell in one organ to embark on a long voyage through the body, spreading through the blood or lymphatic fluid, developing new blood vessels to draw sustenance from its surroundings and overcoming the resistance of immune defenses to infiltrate a new and distant organ, where it will settle and grow into a secondary cancer?
This is the process of cancer metastasis, and it is one of the frontier questions for the biomedicine of the twenty-first century. Ironically, the answer will only be found by asking further and more searching questions. What is special about the few cells that end up colonizing a different organ out of the thousands of millions that, over months or years, make their escape from the original tumor only to be annihilated at some point along the way? Where did they gain the superpowers that allowed them to conquer nature’s resistance? Are these developed over time as the disease advances or are they inbuilt from the start? Why do the cells of a particular tumor only find a ready host in certain other organs?
These are the questions that Joan Massagué has been pondering in far more precise form for many years. A pioneer in the investigation of the genetic and biochemical processes that play a role in metastasis, he is also Spain’s most internationally cited working scientist. Massagué is one of the researchers who best understands the mysteries of metastasis. He refers to it as “a dark forest” through which we are “only just beginning to cut a path,” with the first real insights dating from as recently as “six or seven years ago.” Researching this process is a vital line of attack in the fight against cancer, because metastasis is responsible for ninety percent of the disease’s mortality.
Among the achievements that earned him the BBVA Foundation Frontiers of Knowledge Award in the Biomedicine category was the identification and characterization of the protein known as TGF-beta (transforming growth factor beta). This protein belongs to a large family of factors that regulate the cell division process, and its mechanism sheds important light on the growth patterns of animals and humans. It is essential for the organism’s normal development but, when disrupted, it is also implicated in disease processes such as malformations and cancer.
“In a field as wide as biomedicine, the fact that the jury has singled out my work is an encouragement to my group and to other researchers in oncology,” said a contented Joan Massagué on being informed of the award. What motivates him as a scientist? “We are striving to move forward the frontiers of oncology, starting from the study of very basic aspects like cell biology and behavior, that are perhaps abstruse for most people, in order to address other more concrete points, such as metastasis, so that an area of investigation that yesterday seemed impossible might today look slightly more promising and may in a few years’ time give rise to a solution.”
In the battle against cancer, Massagué’s lab is spearheading the attack. In fact, this is how he himself describes his work on the two processes that are the focus of his research: the metastasis that leads to lung cancer; and the metastasis of breast cancer in the brain, a specially protected organ that is shielded in part from the toxins circulating elsewhere in the body. Specifically, Massagué is co-author of a recent paper describing how the gene ST6GALNAC5 produces an enzyme that is able to coat the surface of invading cells so they go undetected by the brain’s defenses.
But this is just the abbreviated version of a complex story that features a host of factors, and is rife with the long and convoluted names proper to the worlds of genetics and biochemistry. Its language is the language of cells and unfortunately, in Massagué’s view, “what we now understand is only the bare bones of the knowledge that we need.”
It is to acquiring this knowledge that he has devoted all his energy. Massagué is convinced that tackling metastasis calls for an “interactive research effort between clinical and laboratory scientists.” A partnership where one group’s role is to place the information on the table, another’s to identify the genes that tell the tumor cells to metastasize, and yet another’s to develop drugs that block the activity of these genes and stop them setting the tumor cells on the path to metastasis. “Cancer research is a production line,” as he graphically puts it.
The problem is that the production cycle can take 10 to 15 years, the time between the discovery and its publication in a scientific journal and the arrival of a new drug in the oncologist’s arsenal.
But here too Joan Massagué’s work brings grounds for hope. For while it is true that the time-to-market for new therapies may exceed the life expectancy of many patients, it turns out that a number of the genes uncovered by his team and others as having a role in metastasis had also featured in earlier studies on primary tumors. And this means some are already targeted by pharmaceutical drugs that have come successfully through their clinical trials and can be quickly redeployed to attack cancer in its most lethal manifestation.
After completing a bachelor’s degree in pharmacy and PhD in biochemistry at the University of Barcelona, Joan Massagué moved to the United States in 1978 and has lived and worked there ever since. Asked if he might return to Spain some day to continue his research, his answer is succinct: “I already am in Spain. I work between New York and Barcelona.” In New York, 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), an independent, not-for-profit research organization engaging with basic and applied biomedical research. He has more than 340 publications to his name in leading scientific journals, which have been cited more than 62,000 times.
“Metastasis is not just a problem of excessive cell growth, it is above all a problem of cells growing in a place where they shouldn’t be.” Joan Massagué’s place is squarely on the frontiers of knowledge.
