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Develop therapeutics to target oncogenic drivers of solid tumours in children 

Founders' logos
Dr Yaël Mossé

Professor Yaël Mossé, Co-team Lead

Patricia Brophy Professor of Pediatric Oncology

Children’s Hospital of Philadelphia

Prof Martin Eilers

Professor Martin Eilers, Co-team Lead

Professor of Biochemistry and Molecular Biology

University of Würzburg




Austria, France, Germany, UK, US


Cancer Research UK, Institut National Du Cancer (INCa), KiKa (Children Cancer Free Foundation)


structural biology, chemical biology, paediatric oncology, medicinal chemistry

Developing a suite of oncoprotein degraders for childhood solid cancers

Funded by:

KOODAC funders

KOODAC will harness the technologies of targeted protein degradation to target the oncoproteins that drive high-risk childhood solid tumours, with the aim of developing orally bioavailable drugs that will dramatically improve cure rates for children affected by these cancers.  

Cancer remains a leading cause of death by disease in children globally, and progress in the treatment of children with solid tumours has largely stalled. The standard of care for these cancers often relies on decades-old cytotoxic agents and radiotherapy, which can lead to life-threatening toxicities.  

Although the major genetic drivers of childhood cancers have been identified, the proteins encoded by these genes (oncoproteins) have been considered largely undruggable. The oncoprotein drivers of childhood solid tumours are often transcription factors and, with conventional pharmacology, no molecules have been identified that can successfully inhibit their function.  

KOODAC aims to take five key oncoproteins from undruggable to ‘degradable’ with a new generation of compounds called targeted protein degraders that do not inhibit the target protein, but instead degrade it. The team’s overarching aim is to deliver transformative new therapies that can cross the blood-brain barrier and be deployed worldwide for children with solid tumours that are driven by these oncoproteins.

Tackling the Solid Tumours in Children challenge

As part of its programme, KOODAC aims to: 

  1. Target five oncoproteins that drive high-risk paediatric cancers

The team will focus on developing degraders for the ALK, DNAJB1::PRKACA, MYCN, EWSR1::FLI1 and PAX3::FOXO1 (or PAX7::FOXO1) oncoproteins, which have been implicated in the development and/or spread of neuroblastoma, fibrolamellar hepatocellular carcinoma, medulloblastoma, Ewings sarcoma and fusion positive rhabdomyosarcoma, respectively.  

By interrogating the underlying biology of these oncoproteins and understanding how protein degraders act on them, the team will uncover novel insights that could apply to areas beyond the selected paediatric cancers in the future. 

  1. Discover and develop two types of degraders

KOODAC will develop two types of degraders – proteolysis targeting chimeras (PROTACs) and molecular glue degraders (MGDs). Both classes of degraders utilise the cellular ubiquitin-proteasome system, which marks proteins for degradation and leads to cell death.   

The team will develop a platform for the discovery, characterisation and development of degraders for the oncoproteins of interest. Compounds that show promise will enter an optimisation pipeline designed to produce orally bioavailable degraders that can be evaluated in the clinic. 

  1. Conduct clinical studies  

For any promising drug(s) that may emerge from its research, KOODAC will conduct the preclinical studies necessary to enable biomarker-driven clinical trials after the programme is completed. The team aims to develop a framework to deliver phase I clinical studies for evaluation of drug safety and activity. 

By uniting diverse expertise, KOODAC’s vision is to create a new standard of care for children with oncoprotein-driven cancers that that will change the paradigm of paediatric cancer therapy. The team’s patient advocates will work closely with the researchers to advance groundbreaking science and facilitate the clinical utilisation of protein degraders globally.

Dr Yaël Mossé

Professor Yaël Mossé, Co-team Lead

Patricia Brophy Professor of Pediatric Oncology

The Cancer Grand Challenges approach has enabled us to bring together people with very different scientific backgrounds and divergent technological know-how to focus on one overarching question. We feel the responsibility and an urgency to bring better therapies to children with cancer.

Plain language summary

Cancer is caused by errors in a cell’s DNA (the instructions inside a cell that tell the cell what to do). These errors are called mutations, and they can cause cells to produce proteins that aren’t typically found in the cell, known as oncoproteins.  

Oncoproteins can be targeted with drugs to treat cancer, but it’s been difficult to find drugs that can target the oncoproteins in childhood cancers. Team KOODAC will address this problem with a ground-breaking technology called ‘target protein degradation’ and a new generation of drugs called ‘degraders’.  

Degraders can specifically remove oncoproteins from cancer cells via the cell’s existing ‘waste disposal’ system, which dissolves the faulty protein and leads to cancer cell death. Due to their precise targeting of oncoproteins and not normal proteins, degraders are theoretically not toxic, and, unlike many other drugs, they can cross the blood-brain barrier to treat brain tumours. Degraders can also be made available in either a tablet or liquid form, making it easier to distribute them across the world. 

Team KOODAC brings together an interdisciplinary, international team of scientific experts, patient representatives and a committed industry partner, all sharing the vision of developing safe and effective drugs against the previously undruggable oncoproteins of five childhood cancers: neuroblastoma, fibrolamellar hepatocellular carcinoma, medulloblastoma, Ewings Sarcoma and rhabdomyosarcoma. 

Prof Martin Eilers
Dr Yaël Mossé
Dr Alessio Ciulli
Dr Olivier Delattre
Dr. Gwenn Hansen
Dr Charles Kelle
Dr John Maris
Dr Sanford Simon
Dr Seychelle Vos
Dr William Weiss
Dr Georg Winter
Poonam Bagai
Scott Crowther and son Ben
Gavin Lindberg and son Evan
Elana Simon
Leona Knox and son Oscar
Liz and Jay Scott
Macela Zubieta
Sidney Chahonyo
Edie and Emily Gilger