Childhood Cancer Awareness Month: The teams transforming the landscape of paediatric cancer treatment

Cancer remains a leading cause of death by disease among children worldwide. Despite significant advances in medical research, outcomes for some types of childhood cancers, particularly solid tumours, have not improved substantially in more than three decades.

The solid tumours in children challenge is so urgent, we set it in successive rounds, and funded three teams over the two calls. Team NexTGen was funded in 2022, and teams KOODAC and PROTECT in 2024.

The current standard of care for children with solid tumours still relies heavily on cytotoxic chemotherapies and radiotherapy, approaches that are decades-old, and can cause severe and potentially life-threatening side effects. 

Sam Daems, lead patient advocate on team PROTECT and Portfolio Director at Waterland Private Equity emphasises, ‘As children undergo these treatments at the peak of their mental and physical development, the side-effects can, unsurprisingly, be huge.’ 

Many barriers exist to developing specific, effective treatments for children with solid tumours – for example, because adult cancers are very different to childhood ones, therapies that are developed to exploit cancer’s vulnerabilities in adults have limited efficacy in children. Despite this, developing specific treatments for children has also not been prioritised by biopharma.

As Sam puts it, ‘Between 2007 and 2022, only two drugs developed specifically for childhood cancers were approved by the EMA and five by the FDA.’

And that’s not all. Sam explains, ‘Cancer in children and young adults is not a single disease, but comprises a diverse set of illnesses. There are, in fact, 12 main groups which are further split in 47 subgroups, each subgroup further broken down into multiple subdivisions.’

Each of these diseases has unique underlying biology and this specificity also causes issues, with patient populations for each particular disease relatively small. Sam explains, ‘The traditional pharmaceutical industry – where a business model prioritises markets with a higher profit potential – shows limited interest in paediatric oncology which offers an unfavourable risk-return balance.’

Further, smaller patient populations can also slow down recruitment for any clinical trials. To add to this, there is a distinct lack of validated biomarkers for treatment stratification.

A combination of malignancy specific defining mutations, but low overall mutational burden, make prevention impossible. This leaves adequate diagnosis and treatment as the only option for this vulnerable patient population.

Sam Daems, lead patient advocate, PROTECT

While the major genetic drivers of many childhood cancers have been identified, the oncoproteins encoded by these genes have previously been considered ‘undruggable’ using conventional small molecule inhibitors. Furthermore, attempts to target the activity of these oncoproteins indirectly have shown limited, if any, success. 

Much needed new and effective treatments for these cancers will require innovative interventions that specifically target the unique biology of childhood solid tumours. And that’s where our teams come in. Pioneering immunotherapy and targeted protein degradation approaches specifically for young cancer patients, NexTGen, KOODAC and PROTECT hope to transform the therapy landscape for childhood solid tumours, with all three teams hoping to carry out clinical trials. 

Team NexTGen is developing CAR-T cell therapies specifically for children, with a focus on sarcomas and brain tumours. The team’s highly integrated bench-to-bedside strategy will accelerate the development of more potent and effective CAR T-cell products. The team is preparing to begin three clinical trials, where it will test its previously developed approach to gene engineer T cells to resist the immunosuppressive effects of the microenvironment. This is a first in paediatric solid tumour settings and will be tested in combination with the team’s optimised CAR-T cells.

One of the things that was critical for us when we decided to co-fund this team was the opportunity to get clinical data feeding back into the discovery research. At The Mark Foundation for Cancer Research our priority is to make an impact for patients through bringing forward the next wave of discoveries into the clinic.

Ryan Schoenfeld, CEO, The Mark Foundation for Cancer Research, co-funders of team NexTGen

The trials will be carried out simultaneously across the US and UK, with the team analysing results in a centralised manner. This unique approach will allow larger overall cohorts to be included and enable the team to learn from and make the therapies more efficient in real time.

Meanwhile, NexTGen's patient advocates are working with the researchers in the team to ensure that the complex challenges of obtaining, sharing and maximising the use of the precious tumour samples gifted by parents and/or patients is managed appropriately.  

Team KOODAC is focused on developing targeted protein degraders against five key oncoproteins implicated in driving neuroblastoma, fibrolamellar hepatocellular carcinoma, medulloblastoma, Ewing’s sarcoma and fusion-positive rhabdomyosarcoma. These are all cancers of high unmet need, with no targeted therapies available. 

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.

Yaël Mossé, Co-Team lead, KOODAC, Children's Hospital of Philadelphia 

Integral to the team’s mission, KOODAC’s patient advocates will work closely with the researchers, providing insights and guidance to advance this cutting-edge science from the laboratory setting toward clinical implementation. Their perspectives will be crucial in facilitating the global translation of protein degraders, to improve outcomes and quality of life for young patients. The patient advocates are already working to help identify potential patients for future clinical trials. 

Team PROTECT is also utilising targeted protein degradation approaches focusing on targets known to be essential for the development of Ewings sarcoma, neuroblastoma, synovial cell sarcoma, high-grade glioma, ependymoma and gastrointestinal stromal tumours. In addition, team PROTECT is exploring combination strategies where drugs with oncogene degrader capability for controlling tumour growth will also synergistically regulate CAR expression or function in T cells, thereby acting as CAR ‘ON’ or ‘OFF’ switches. This will allow for periods of rest from CAR signalling, in the hopes of combating T-cell exhaustion and improving outcomes.  

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.

Stefan Pfister, Team Lead, PROTECT, German Cancer Research Center (DKFZ) 

The team’s patient advocates will play a crucial role in translating the research, helping to build a sustainable business model and influencing policymakers to encourage greater investment and support for paediatric cancer drug development. Sam will be instrumental to this, leading the business development side.  

Quotes from Sam Daems were taken from this piece that he wrote for Cancer Research UK.

Sam Daems

Sam is Portfolio Director at Waterland Private Equity where he evaluates investments, structures transactions, and supports companies in defining and executing their strategy. Additionally, he conducts research on innovative business models to develop therapeutics for ultra-rare diseases at Université Libre de Bruxelles Institute for Interdisciplinary Innovation in Healthcare. He is a member of the  PROTECT Cancer Grand Challenges team, acting both as a Patient Advocate and workstream lead.

Team NexTGen is funded by Cancer Research UK, the National Cancer Institute and The Mark Foundation for Cancer Research through Cancer Grand Challenges.

Team KOODAC is funded by Cancer Research UK, Institut National Du Cancer and KiKa (Children Cancer Free Foundation) through Cancer Grand Challenges.

Team PROTECT is funded by Cancer Research UK, the National Cancer Institute, the Scientific Foundation of the Spanish Association Against Cancer and KiKa (Children Cancer Free Foundation) through Cancer Grand Challenges.