University of Zurich: Curing Cancer in Children

Ana Guerreiro Stücklin: “Survival rates for brain tumors have improved, but not as markedly as for other childhood cancers such as leukemia or kidney tumors.” (Image: Dan Cermak)

“Far too many children still die from brain tumors,” says oncologist Ana Guerreiro Stücklin. “It’s clear we still haven’t found the best therapy for many tumors.” And this is precisely why the 40-year-old does what she does day in, day out – trying to find the best possible therapy for her young patients.

Ana Guerreiro Stücklin is a physician at the University Children’s Hospital Zurich, where she treats young patients suffering from brain tumors. This generally involves a combination of surgical procedures, chemo and radiotherapy, and in some cases also experimental treatment options. The aim is to slow down the tumors’ growth, or stop it altogether.

Diverse biology of tumors
Unfortunately, the biology of tumors is very diverse, and some malignant growths respond to therapy better than others. The number of children who succumb to brain tumors is lower than it was 20 years ago, but the disease still ends in death in 20% to 30% of cases.

“Survival chances may have increased,” says Ana Guerreiro Stücklin, “but not as significantly as in other types of childhood cancer, such as leukemia or kidney tumors.” After leukemia, brain tumors are the second most common cancer in children, and today more children die from brain tumors than blood cancer.

What does and doesn’t work
The children who do survive often have to live with side effects and other diseases later on in their lives, including cognitive developmental disorders, infertility or subsequent cancers. Ana Guerreiro Stücklin knows the effects, side effects and limitations of the most common therapies from first-hand experience. She sees up close in her young patients what does and doesn’t work.

At the same time, her work in the lab is laying the groundwork for improving these very therapies. To achieve this, she needs to better understand how tumors develop and why they grow.

Thanks to considerable advances in genomics, researchers are getting better and better at characterizing cancer cells. “And yet, we now also see that tumors that used to be grouped together under the same name can be very different in their biology and clinical progression,” says the UZH oncologist. “The biology of tumors is so complex that finding the answer to one question often opens the door to a host of new ones.”

Fighting cancer on two fronts
One example of this came during a recent international collaboration. Together with her peers, Ana Guerreiro Stücklin discovered that a specific type of brain tumor in infants develops as a result of gene fusion. This fusion leads to an abnormal hyperfunctional protein, which drives cell growth and causes cancer cells to develop.

“If we understand this mechanism,” explains Guerreiro Stücklin, “we can target the specific cancer cells.” Encouragingly, this type of gene fusion appears to be highly susceptible to targeted therapy.

The pediatrician is fighting cancer on two fronts, so to speak. She wants to improve her understanding of the disease and at the same time use this knowledge to better target her treatment. This ambitious plan started with an MD-PhD program at UZH, which enables medical students and graduates to combine their medical skills with a second course of study in the natural sciences.

From there, her path took her to the University Children’s Hospital Zurich and then to the University of Toronto’s Hospital for Sick Children. Two years ago, she rejoined the University Children’s Hospital, where she has since established her own research group thanks to an SNSF Eccellenza Fellowship. In 2020, Ana Guerreiro Stücklin also received a fellowship from the “Fonds zur Förderung des akademischen Nachwuchses der UZH” (FAN).

The fortitude of the young patients
The time she spends with patients motivates her work as a researcher. “My everyday work in the clinic makes me realize how important research is,” she says. “I often get asked by parents: Isn’t there anything more we can do?” She greatly enjoys working with her young patients. “With all the problems and struggles they’re going through, I’m constantly amazed at the fortitude of these children, and how despite everything they manage to live life to the full with the curiosity and exuberance typical of all children.”

The relationships that develop with her patients and their families are often lasting. “We support the children all their lives. It’s very moving and rewarding,” says Ana Guerreiro Stücklin. This long-term care aims to detect any negative consequences of therapy or relapses as early as possible. And the children and youngsters often need support when it comes to rejoining school or entering the world of work.

No “magic bullet” yet
Even when cancer is defeated, it leaves its mark – inside the children’s bodies and later on in their lives. One of the reasons for this is that chemotherapy still isn’t specific enough. There is no such thing (yet) as a “magic bullet” that can strike at the heart of the disease. This idea dates back to German physician and Nobel laureate Paul Ehrlich, who coined the term over a century ago and stated: “We have to learn how to aim chemically.”

Ana Guerreiro Stücklin shares this view – and is determined to hit the mark. “There are many drugs that can inhibit a wide variety of proteins,” she says. The oncologist intends to find out which ones work in which ways, and where they can be deployed to maximum effect. To succeed, she will rely on qualities that she deems essential, such as patience, perseverance and above all, a healthy dose of optimism: “You have to know when to walk and when to run.”