Cancer in the Bones

Anyone who elects to go toe-to-toe with sarcomas has picked a tenacious adversary. The malignant tumors originate in bone or soft tissues and primarily afflict young people. Sarcomas account for around 20% of all tumors in children and adolescents but for only around 1% in adults. Several dozen different sarcoma subtypes exist, which complicates research in this area. Moreover, cancers in children and adolescents are different from those in adults.

“The changes that these cancers cause differ by subtype. Specific treatment approaches are needed for each one,” says UZH Professor Didier Surdez, who heads the bone sarcoma research unit at Balgrist University Hospital and is involved in Switzerland’s National Center of Competence in Research (NCCR) Children & Cancer.

Targeted therapies and immunotherapies have radically transformed cancer medicine in recent years. They have brought tremendous advancements for many cancer sufferers, particularly in the most common adulthood cancerous diseases. Unfortunately, most sarcomas, including those in children and young adults, thus far have not been fightable to the same extent with these new therapies. This is because the tumors often find ways to evade the immune system, or they exhibit genetic mutations that are hard to treat in a targeted manner.

Moreover, since sarcomas are rare diseases, the pharmaceutical industry has invested comparatively little to date in developing specific therapies for them. That’s why medicine continues to rely mainly on surgery, chemotherapy and radiation therapy to treat sarcoma patients. However, these treatments can cause side effects that impair the quality of life of young patients long after the end of therapy. Plus, they are not always effective, particularly not if the cancer returns or has spread to other areas of the body.

To find new treatment options for these patients, the team led by Surdez has developed a research program that it uses to optimize patient-based tumor models in the laboratory. The aim is to identify and map the biological properties of the original tumors as precisely as possible. “Most tumors are composed of multiple different cell types. Our models map part of this complexity, and they are also capable of replicating the three-dimensional interactions between the cells in some tumors,” Surdez explains. “We have succeeded in producing models of this kind for several aggressive sarcoma subtypes in the laboratory, and we’re now using them to test potential drugs,” he adds.

Using this approach, the team has already identified a class of molecules capable of selectively killing one specific sarcoma subtype. This lays a solid scientific foundation for further drug development and potential future clinical trials.

Beyond the quest for new drugs, optimized tumor models are also valuable for gaining a better understanding of how tumors evolve over time. “Many existing methods yield only a snapshot,” the researcher says, “but a single picture tells us nothing about the progression over time.” With the aid of the models, however, researchers can observe how cancer cells interact with each other and adapt themselves.

Another core aim of Surdez’s research is to identify high-risk groups among patients on the basis of genetic traits, i.e. by means of attributes that cannot be captured by standard clinical criteria such as tumor size, presence of metastases or patient age. That information could help therapy teams to get a better read on patients and choose the most suitable treatment strategy for each person.

Since sarcomas are rare, international research cooperation is crucial because it takes hundreds of cases to conduct meaningful studies. Researchers sharing data across institutional and national boundaries is working better and better, Surdez says, adding that it’s important for the NCCR Children & Cancer to give additional impetus now also in Switzerland.

He heads the program’s subdomain focused on identifying new therapeutic vulnerabilities in childhood cancers and on better characterizing the different types of cells in the tumors, with the clear objective of enabling better treatment for cancer sufferers. “We occasionally get to meet patients and their families,” Surdez says. “Those encounters are always extremely moving and highlight why we do our work.”