The Paediatric Therapeutic Development Workshops are a joint initiative between LifeArc, Innovative Therapies for Children and Adolescents with Cancer (ITCC), Cancer Research UK, Cancer Research Horizons and the Cancer Grand Challenges PROTECT team. The workshops bring together childhood cancer experts, including patient advocates, to help identify the most urgent needs and promising treatment ideas. The aim is to speed up progress by prioritising promising options, allowing the research community and funders to help drive future progress in a more streamlined way. In early 2025, a workshop was hosted on osteosarcoma. 

Before the workshop, participants received a detailed document explaining what we currently know about osteosarcoma in children and young adults and a list of drug targets and treatments currently in development. Patient advocates set the scene, by explaining the patient experience with current clinical practice and share their views on the priorities for improving treatments.  

Osteosarcomas are the most common type of bone cancer in children and young adults under 25, usually developing in bones of the leg or upper arm during growth spurts. They are thought to be caused when bone cells, or cells that are pre-programmed to become bone cells, develop genetic mistakes that cause them to grow and divide out of control.  

At the workshop, the group selected molecules found in osteosarcomas that should be prioritised as potential targets for new drugs. These included: 

1. LRRC15: this molecule is found at much higher amounts in osteosarcoma cells than in healthy tissues. LRRC15 sits on the surface of osteosarcoma cells, making it an ideal target for drugs like antibodies, which can hunt down molecules on the outside of cells.  
2. SMARCAL1: Some osteosarcomas rely on this molecule to help protect the cancer cells’ DNA against damage caused when the cells grow and divide, making it a vulnerability in osteosarcoma. By inhibiting or breaking down SMARCAL1 with a drug, the cancer cells, and not healthy cells, accumulate excessive DNA damage, forcing them to stop growing.  
3. ROR2: this molecule helps to control normal bone and muscle development. It’s found in much higher amounts in osteosarcoma tumours than in normal tissue. It was also identified as a high priority target in a Paediatric Therapeutic Development Workshop on rhabdomyosarcoma and could be targeted with an antibody.  
4. KIF18A: Some osteosarcomas have ‘genome duplication’ where there are multiple copies of all the genetic material inside the cell, instead of just one. Cancer cells that have undergone this process are thought to rely on KIF18A for survival, but healthy cells do not. There is good evidence of this in other cancer types, but more research is needed to know if blocking this molecule in osteosarcoma cells could help tackle the cancer. 
5. EIF4A1: this molecule helps cells to make proteins – molecules required to carry out vital functions inside cells. EIF4A1 is  found in higher amounts in samples from people with osteosarcoma. Laboratory tests have also shown that osteosarcoma cells are dependent on EIF4A1 to be able to grow –  targeting it with a drug that can inhibit its action may stop the cancer cells in their tracks.
6. RUNX2: this target controls how normal bone cells grow and mature into bone tissue. It’s present in higher amounts in osteosarcoma samples, particularly in tumours that are resistant to chemotherapy. 

In addition to these top six targets, MYC, a known driver of many cancers, is a high priority in osteosarcoma and is being explored for other childhood cancers. 

In order to survive, all cells, including cancer cells, need to be able to repair damage to their DNA. Osteosarcoma tumours have impaired DNA repair mechanisms and are highly dependent on any remaining, working, mechanisms to survive. Identifying and blocking the components of these remaining mechanisms is another priority area to explore. Knocking out their ability to repair DNA damage all together, would remove their ability to survive.  

The workshop also highlighted additional molecules that could be targeted with existing antibody-based treatments (antibody drug conjujugates). With these drugs, the antibody is able to track down the cancer cells and then deliver cancer drugs directly to them. Promising targets include B7‑H3, GPC2 and GD2, which are already of interest for other children’s cancers and could also be targeted with CAR-T cell therapy – where the bodies own T cells, a type of white blood cell, are reprogramed to recognise and destroy cancer cells.

The outcomes of this workshop can now be used by the research community and funders to help drive focused progress, together. The response to the workshop has also shown how much the community values this approach. We now believe there is appetite to build on this work moving forward, incorporating the innovative approaches and tools developed through these workshops. Investigators can apply for further support from projects like C‑Further – a partnership between LifeArc, Cancer Research Horizons, and Great Ormond Street Hospital Charity – which focuses on developing new medicines specifically for children with cancer.