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Develop therapeutics to target oncogenic drivers of solid tumours in children 

Founders' logos
Dr Stefan Pfister

Professor Stefan Pfister, Team Lead

Professor of Pediatrics

Hopp Children's Cancer Center Heidelberg (KiTZ)




Germany, the Netherlands, Spain, UK, US


Cancer Research UK, National Cancer Institute, the Spanish Association Against Cancer, KiKa (Children Cancer Free Foundation)


paediatric oncology, targeted protein degradation, high-throughput chemical screening, medicinal chemistry, structural biology, tumour biology, preclinical drug testing, clinical trials

Harnessing protein degradation for advanced childhood tumours

Funded by:

PROTECT funders

Team PROTECT aims to establish a platform to develop and test drugs targeting the undrugged drivers of childhood solid tumours, with the vision to develop the next generation of therapeutic approaches for children with cancers of unmet clinical need. 

Survival rates for children with solid tumours, including brain tumours, have largely stagnated over the past 30 years. Cures for these cancers will require innovative interventions that specifically target the unique biology of childhood solid tumours. With advances in targeted protein degradation and chemical interventions to inhibit protein-protein interactions, it has recently become tractable to target the oncoprotein drivers of childhood cancers that were previously thought to be ‘undruggable’.  

To fuel the next wave of improvements in childhood cancer outcomes, Team PROTECT will utilise innovative approaches involving targeted protein degradation to target the undrugged drivers of childhood cancers of high unmet clinical need, as well as explore ways to improve the efficacy of chimeric antigen receptor (CAR) T-cell therapy.  

By developing a sustainable platform that will result in a ‘pipeline’ of paediatric-specific drug development candidates, the team aims to provide a blueprint to apply targeted protein degradation and other novel approaches including multi-modal combinations to target the most challenging childhood cancer targets. 

Tackling the Solid tumours in children challenge

PROTECT’s work will cover three overarching and interacting themes: 

  1. Identify drugs against targets of interest

To improve the chances of getting at least one asset into clinical application, the team will take a broad approach by focusing on a variety of targets at different levels of development that are known to be essential for the development of Ewings sarcoma, neuroblastoma, synovial cell sarcoma, high grade glioma, ependymoma and gastrointestinal stromal tumours.  

For some of the targets, drug candidates already exist. For the targets without existing drug candidates, the team will dissect their chemical structure, and apply ligand discovery, fragment-based screening and optimisation approaches to identify drug candidates against them. The main group of drugs that the team will explore is targeted protein degraders, which bind to tumour-specific proteins and degrade them. 

For the targets with drug candidates that show potential, the team will use its collection of in vivo models to assess dosing, scheduling and toxicity as well as combinations. 

  1. Improve responses and therapeutic window of CAR T-cell therapies

CAR T-cell therapy has shown great promise in treating blood cancers, including those in children; however, it has had limited success in solid tumours. One limitation of CAR T-cell therapy is that the CAR T cells can become ‘exhausted’, which impairs their cancer-killing ability.  

To combat this problem, Team PROTECT will deploy targeted protein degradation approaches to develop treatment strategies that act as an ‘ON’ or ‘OFF’ switch to regulate the activity of CAR-T cells.  

  1. Deliver early-phase clinical trials

PROTECT’s goal will be to use their emerging data to prioritise only the most promising drugs, moving these as far along the translational pipeline as possible. Working with industry partners, the team will make all efforts to move the most promising drugs into the clinic, with the aim of delivering at least one optimised protein degrader for its application in early-phase clinical trials in the context of the PROTECT project.    

The team’s patient advocates will be instrumental in achieving PROTECT’s goals and will help to build a business model and influence policy makers to encourage greater investment and support for specific drug development for paediatric cancers. 

Dr Stefan Pfister

Professor Stefan Pfister, Team Lead

Professor of Pediatrics

This academic team approach to drug discovery for paediatric-specific therapies will be essential to increase cure rates for some of the most challenging cancers in children and decrease lifelong sequelae.

Plain language summary

While recent developments in cancer therapies have brought hope and even cures to many adults with cancer, children have had much less access to novel treatment options. Treatments in children have often relied on repurposing drugs originally designed for adult cancers. Childhood cancers, however, are very different from those in adults, and therefore require the development of new drugs that target their unique biology.  

Recent advances in understanding the biology of childhood cancers have unlocked new ways to target these cancers. In addition, there have been innovative developments in an approach called ‘targeted protein degradation’, in which drugs are developed that lead to a breakdown of cancer-specific proteins. This approach is enabling new ways to reach the previously undruggable proteins in childhood cancers.  

Based on these recent advances, PROTECT aims to develop the next generation of treatments for children with solid cancers, including brain tumours. 

PROTECT will focus on seven different childhood cancers and will test drug candidates that are at different stages of the drug development pipeline. As well as finding new drugs, the team will also work to find ways to make an existing therapy, called CAR T-cell therapy, work better. CAR T-cell therapy harnesses the power of the body’s immune system to fight cancer. It has shown success in the treatment of some types of blood cancer, but the same success has not yet been seen in solid tumours. 

The team will prioritise the most promising targets and drugs, testing their safety and success in laboratory experiments. PROTECT will aim to move the most promising drugs into early-stage clinical trials.  

As part of the project, PROTECT’s patient advocates will aim to build new business models and work with policy makers to find ways to increase investment in drug development for childhood cancers. 

Dr Stefan Pfister
Dr John Anderson
Dr Scott Armstrong
Dr Ana Banito
Dr Louis Chesler
Dr Florencia Cidre-Aranaz
Dr Benjamin Ebert
Dr. Eric Fischer
Dr Volker Germaschewski
Nathanael Gray
Professor Swen Hoelder
Dr Max Jan
Dr Cigall Kadoch
Dr Cristina Mayor-Ruiz
Dr Kimberly Stegmaier (photo credit Sam Ogden)
Frank von Delft
Dr Frank Westermann
Dr Judith Wienke
Patricia Blanc
Sam Daems
Delphine Heenen