Using first-in-class mRNA export inhibitors to treat childhood cancer

The challenge

Cancer remains the leading cause of disease-related death in Australian children. For aggressive childhood cancers such as osteosarcoma, neuroblastoma, medulloblastoma, and rhabdomyosarcoma, survival rates have changed little for decades.

Children with these cancers endure long and intensive treatment involving surgery, chemotherapy, and radiotherapy. While these treatments can save lives, they often cause lasting side effects that affect growth, learning, fertility, and heart health. For children whose cancers return after treatment, options are limited, and outcomes are poor.

A major reason for this lack of progress is that childhood cancers differ biologically from adult cancers. Many medicines developed for adult cancers target particular genetic changes, but these changes are less common in childhood tumours. There is an urgent need for new treatments designed for children’s cancers that are both effective and less toxic.

The research

Prof Wickramasinghe and his team are investigating a possible new treatment approach for childhood cancers. Their research focuses on a process called mRNA export. This process helps genetic instructions move from the cell’s control centre to the part of the cell where proteins are made, called the cytoplasm. This process is essential for all cells to survive and grow, but some cancer cells depend on it much more than normal cells do. When this pathway is blocked, cancer cells die while healthy cells can adapt and survive. This selective vulnerability offers a new opportunity to attack tumour cells without harming normal tissue.

This project will determine which childhood cancers are most dependent on mRNA export pathways and whether this weakness can be targeted using a new class of pill-based inhibitors developed by Prof Wickramasinghe and Prof Lessene. These compounds block the export process, stopping the cancer cell’s ability to make vital proteins and causing the cell to die.

The team will work closely with the lived experience committee at the Hudson Institute of Medical Research to ensure the research reflects the priorities of families affected by childhood cancer. This continuous engagement will ensure that the team’s research remains grounded in the lived experience of families and focused on outcomes that matter most, by developing treatments that are more effective, less toxic, and that allow children with cancer to live longer, healthier, and more normal lives.

The impact

If successful, this project could identify a novel therapeutic pathway capable of selectively killing tumour cells while sparing healthy ones.

A major advantage of this approach is that the inhibitors are pill-based treatments that can be taken at home, reducing invasive procedures and disruption to daily life. For families in regional/remote communities, oral therapies would also reduce the burden of travel and hospital stays.

This is early-stage research. Promising results would then need to be followed by further laboratory studies and clinical trials before any new treatment could be offered to children. In the longer term, the work could help support the development of more precise and less toxic treatments for childhood cancer.

Children's Cancer CoLab Funding Information

Grant Awarded (Total): $500,897
Project Timeline: 1 September 2026 – 31 August 2028
‍Impact Program: Transformative Therapies (formerly Next-Generation Therapies)‍
Lead Institution: WEHI
Collaborating Institutions: Hudson Institute of Medical Research
Lead Researcher: Prof Vihandha Wickramasinghe
Associated Researchers: ‍Prof Guillaume Lessene and Prof Ron Firestein