EPFL joins national effort against childhood cancer

Childhood cancer is not a single disease. It encompasses many rare diseases, each presenting its own biological and clinical challenges. Brain tumors alone comprise more than 100 distinct entities, making collaboration between researchers and clinicians essential.

This is the idea behind NCCR Children & Cancer, a 12-year national research program bringing together expertise across Switzerland, from fundamental cancer biology and metabolism to diagnostics and immunotherapy.

“Childhood cancers are many rare diseases, which require expertise at many different levels,” says Sebastian Waszak, head of EPFL’s Laboratory of Computational Neuro-Oncology and EPFL representative on the NCCR’s national steering committee. “Research into rare cancers is often driven by single labs in Switzerland. Now we are joining forces across more than 30 research groups, with a shared agenda and roadmap.”

Along with Waszak, another three EPFL researchers will contribute to the project: Fides Zenk, Christoph Merten, and Li Tang. Their expertise ranges from neural organoids and immunotherapy to miniaturized drug-testing systems, genomics, and computational biology.

“We will use new technologies to study the molecular mechanisms of childhood cancers and to improve their diagnosis,” says Waszak. “We need different institutions, from technical universities to hospitals, to work together to advance our understanding of these diseases and develop novel therapeutic options.”

Following tumors over time

Waszak leads one of the NCCR working groups studying how tumors change across space and time. His team focuses on high-grade gliomas, a diverse family of brain tumors that present a particular challenge.

“These don’t necessarily form a single tumor mass. Instead, they spread diffusely into healthy brain tissue,” he explains. “Taking repeated tissue biopsies is challenging because tumor cells are often located deep within the brain.”

After an initial tissue biopsy or surgery, pediatric neuro-oncologists therefore rely on MRI to monitor the disease. Waszak’s group is investigating another source of information: small fragments of circulating tumor DNA that can be found in spinal fluid.

By studying cell-free DNA, his group aims to identify the part originating from brain tumors and track how its molecular characteristics change during treatment.

“What is promising about liquid biopsy is that it gives us more than a one-time snapshot of cancer genomes,” says Waszak. “By analyzing cell-free DNA genomes and methylomes, we want to track how tumors change over time and adapt to therapy.”

Recreating cancer development

Fides Zenk’s group will approach childhood brain tumors from another direction, using neural organoids to recreate how they arise during human development.

The models will allow researchers to reconstruct the molecular paths cells take from normal development toward cancer and provide a system for testing possible therapeutic strategies.

“To understand how to treat childhood brain cancers, we need to understand how they emerge from normal development,” says Zenk. “By recreating this process in neural organoids, we hope to uncover when and how cells take the wrong path and identify vulnerabilities that could ultimately be targeted therapeutically.”

Testing treatments before therapy begins

Christoph Merten’s group will develop miniaturized assay systems to test how tumor cells from individual patients respond to different drugs.

The goal is to identify the treatment most likely to work before therapy begins, while avoiding drugs that are ineffective or unnecessarily toxic.

“If we could replace trial-and-error therapies with more efficient and less toxic medications, that would be great,” says Merten. For translating microfluidic drug response profiling into a clinical reality, Merten also co-founded the EPFL spinoff TheraMe!, developing benchtop instruments for personalized cancer therapies.

Engineering smarter immune cells

Li Tang’s group will develop a new generation of CAR-T cells, a form of living therapy in which a patient’s own immune cells are reprogrammed to recognize and attack cancer.

The researchers aim to engineer CAR-T cells that coordinate several immune responses and recognize more than one tumor marker. This could help prevent cancers from escaping treatment by losing the single marker targeted by current CAR-T therapies.

“Together with Francesco Ceppi at CHUV and the other NCCR partners, we want to build cell therapies that give real options to children with aggressive cancers that today leave very few,” says Tang, including relapsed or treatment-resistant leukemia, lymphoma, brain tumors, neuroblastoma and other solid tumors.

Toward precision medicine for children

For Waszak, these different approaches ultimately converge on a common goal: giving each child treatment options based on the biology of their disease.

Brain tumors in children and young adults are highly diverse. Genetic alterations help define individual tumor entities and can influence whether a tumor responds to therapies.

“We know from clinical studies that, depending on the specific tumor type, a patient may respond very differently to standard-of-care and targeted therapies,” says Waszak. “We need to characterize pediatric brain tumors at several molecular layers and use all available information to map out potential targets. Novel assays such as cell-free DNA methylation sequencing have the potential to capture much of this molecular diversity in one go.”

A translational goal of the NCCR is to establish a platform for precision oncology for childhood cancers in Switzerland, bringing specialists together to examine individual cases using advanced molecular information within multidisciplinary tumor boards.

“Right now, there is no dedicated precision medicine program available for patients with childhood cancers,” says Waszak. “Our goal within the NCCR is to develop the technological foundation that would give patients in Switzerland access to advanced molecular diagnostics and targeted treatment options.”