Evaluation and optimization of drug combinations that kill neuroblastoma cancer cells

The challenge

Current chemotherapies are not effective enough for around one in two neuroblastoma patients, leaving them with a low chance of survival. Children that do survive their cancer often experience side-effects and health problems later in life due to the toxicity of many chemotherapies used currently. There is therefore an urgent need for new and more targeted treatments. 

Recent research has shown that neuroblastoma cells are highly sensitive to a type of drug that can alter how cells make messenger RNA (mRNA) – a molecule that carries the ‘recipes’ for making the proteins needed inside the cell. Tumours such as neuroblastoma are more sensitive to the mRNA-altering drugs than healthy normal cells, because cancer cells require very specific mRNA configurations to help their rapid growth. 

The project

In this project, Professor Karim Malik and his team at the University of Bristol will assess whether a specific combination of mRNA-altering drugs and DNA repair inhibitors is an effective therapy for neuroblastoma. Early work from his group strongly suggests that neuroblastoma cell require certain essential mRNA configurations to survive DNA damage, which can occur as a consequence of the rapid growth of cancer cells. Inhibiting certain mRNA configurations will result in cancer cells accumulating DNA damage, leading to cell death. By combining drugs that alter mRNAs with drugs that prevent DNA repair, tumour cells will be unable to tolerate the high levels of DNA damage and die.

The impact

This project is developing a combination treatment with drugs that are already in clinical trials – which means that any effective new treatment could be introduced much more quickly than a brand-new medicine. By using a combination of drugs, the researchers also hope to prevent drug resistance and enable lower doses for patient, which would limit potential side effects. If successful, Professor Malik hopes to see clinical trials of the proposed drug combination within five to 10 years, introducing a safe and effective new neuroblastoma treatment.