Adnkronos (Adnkronos) – Cancer doesn't grow in a vacuum. Surrounding diseased cells is an environment made up of support cells, immune cells, and a dense network of fibers, the extracellular matrix, which the tumor modifies and bends to its own interests. And it's not just who inhabits this environment that matters, but also its consistency: a dense, rigid matrix can make the tumor more aggressive, promote metastasis, and block the path to treatment.
This new frontier in tumor mechanobiology is the focus of the 8th Translational Oncology Workshop, which will bring together international experts at the Regina Elena National Cancer Institute (IRE) in Rome on October 19 and 20, in collaboration with the Manchester Cell-Matrix Centre at the University of Manchester and the Cancer Research UK Manchester Institute. The new challenge in the fight against cancer, therefore, is to overcome the invisible walls that protect it.
For a long time, the extracellular matrix, the material that fills the space between cells, was considered a simple scaffolding, explain the researchers from Regina Elena.
Today we know this isn't the case. It's a dynamic structure, continually built and remodeled, and in tumors, it influences cell behavior. It can be denser or looser, stiffer or softer, and cells sense it. It's as if they possess a sense of touch: they perceive the hardness of their surroundings and transform it into signals that regulate the activity of genes involved in tumor growth, its ability to invade other tissues, and its resistance to treatment.
And between the tumor and the cells surrounding it, messages travel in both directions. "It's a continuous dialogue, in which the tumor and the microenvironment reinforce each other," explains Giovanni Blandino, scientific director of the Regina Elena Institute. "For decades, we've been attacking the tumor cell. Tomorrow's therapies will have to interrupt this exchange as well." Interrupting, however, doesn't mean destroying everything: "Not all the cells surrounding the tumor work for it; some fight it," Blandino points out. "This is the case with some fibroblasts, the cells that produce the matrix: some favor the tumor, others slow it down. The latter must be strengthened, not eliminated. We must be selective."
Pancreatic cancer is the most emblematic example, experts explain. It is often surrounded by fibrous tissue so dense that it hinders the distribution of drugs and the action of immune cells. This environment is defined immunologically as "cold," in which the body's defenses struggle to function and even immunotherapy encounters significant difficulties. In head and neck and ovarian cancers, the extracellular matrix can also contribute to disease progression and treatment resistance. In head and neck cancers, researchers are also studying whether matrix rigidity in the surgical area can influence the risk of recurrence. IRE researchers are also working on these issues, conducting dedicated studies.
Last year, the Translational Oncology Workshop highlighted the alliances that tumors form with their microenvironment, according to a press release from the IRE. This year, it examines them with a more powerful magnifying glass. Thanks to spatial molecular analyses, imaging technologies, and three-dimensional models, scientists can more precisely study the interactions between tumor cells, the matrix, and the immune system, searching for new biological markers and potential therapeutic targets.
"These events reflect the Institute's strategic objectives," says Livio De Angelis, Director General of the IFO, the Hospital Physiotherapy Institutes that include the Regina Elena Hospital: "Strengthening international collaborations, investing in young talent, and accelerating the translation of research findings into treatment. This is how an IRCCS builds innovation at the service of patients."
The two-day event is organized by Blandino, Anna Bagnato, and Paola Nisticò of the Regina Elena Institute, along with Adam Byron of the University of Manchester and Claus Jørgensen, deputy director of the Cancer Research UK Manchester Institute. Speakers include world-class experts such as Valerie Weaver of the University of California, San Francisco, and Amanda Psyrri, an oncologist at the University of Athens, who is involved in the clinical trials. Ample space is given to young researchers, many of whom are from the IRE.
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