After research on cancer cells has revolutionized cancer treatments in the last 25 years, Joan Massagué believes that the time has come to go one step further. “To continue improving treatments, we face the colossal challenge of understanding not only what are the effects of genetic mutations on tumor cells, but also how cells interact with the whole organism; we have to go beyond genomics”, declares the Catalan scientist, who directs the Sloan Kettering Institute for cancer research in New York.
To advance towards this goal, Massagué has led the creation of the Kravis Cancer Ecosystems Project, funded by the Marie-Josée and Henry R. Kravis Foundation with one hundred million dollars for the next ten years.
Is genetics no longer enough to continue improving treatments?
We are facing a paradigm shift in cancer research. Targeted therapies, based on genetic alterations of tumor cells, have revolutionized cancer treatments, but they have a ceiling. At the same time that these therapies have been developed and we have become aware of their limits, we have begun to better understand the importance of what happens in the environment of cancer cells.
Does the evolution of a cancer depend on its environment?
There are many cells that have carcinogenic mutations, but very few have the ability to cause a tumor. Mutations are necessary but not sufficient for cancer to start. Both the origin and the progression of tumors depend to a great extent on the ecosystem of the local tissue, the organ and the organism as a whole.
What exactly does it depend on?
The microenvironment of the tumor is important, but so are the immunity of the organism, the intestinal microbiota, metabolism, inflammation... Targeted therapies have dominated the research landscape so much in recent years that they have eclipsed this other part, which we see increasingly clear that it is also important. Now we can begin to ask ourselves concrete questions that we can answer.
How can all this be translated into new treatments?
Immunotherapy, which has been introduced in recent years and successfully treats certain types of cancer, shows us the way. It is not a treatment that directly attacks the cancer cell, but instead stimulates the body's natural immune cells to attack the tumor.
You talked about inflammation and metabolism. Could some drugs already approved for other indications be useful for cancer treatments?
Absolutely. We need to better understand how tumors interact with the body. But it is very possible that, for some patients who present certain metabolic or infectious conditions, we can reduce the probability of recurrence with existing drugs.
With a hundred million dollars available, where do you plan to start?
Most of the questions we have now pose colossal challenges. For example, how do metastases manage to evade immunity? What is the role of the intestinal microbiota in the progression of tumors? How does cancer exploit the body's natural mechanisms of regeneration and repair? We cannot expect any single laboratory to be able to answer these big questions on its own. We are going to have to organize ourselves so that different laboratories collaborate from the beginning pursuing the same objective.
Will the priority be to improve treatments?
Improving patient care is the ultimate goal, but for this we must support basic research, which is a source of new ideas. In my institution we are very clear that it would be a serious mistake to reduce basic research. In many of our laboratories, basic science coexists with translational research directed at cancer. Our goal is not just to find the next short-term therapy. It is also laying the foundations for the improvements that must come in the medium and long term.
What will be the first big question they will address?
It's not decided yet. We will open a call for Sloan Kettering teams, who will be able to collaborate with scientists from other institutions, and we will have an external advisory committee to evaluate them. Not many proposals will be approved. For them to have the funding they need, they have to be few and very powerful.
Could researchers from Spanish institutions participate in any of these projects?
Why not? The idea is that four or five research groups collaborate on each project. The projects will be coordinated from Sloan Kettering, but if there are researchers at other institutions that we consider to be key, they will be invited to participate. If any of them work in a research center in Spain, it would not be an obstacle.
