Researchers at the University of East Anglia have developed a new drug that works against bone cancer including osteosarcoma (OS). The drug, called CADD522, has shown promising results in the laboratory. It will now undergo formal toxicology assessment before hopefully entering a clinical trial.

The development of CADD522

To develop a drug you first need to identify a target. The researchers of this project were interested in how non-coding RNAs may be involved in bone cancer. Non-coding RNAs are present in all living cells and can regulate genes. They looked at non-coding RNAs in people with chondrosarcoma (CS), a type of bone cancer. Several small non-coding RNAs were identified as possible cancer drivers. These were looked at further in a 3D cancer model. The levels of one small non-coding RNA called miR-140 were seen to increase during cancer progression. This non-coding RNA was known to regulate a gene called RUNX2. The researchers found that increased levels of RUNX2 aided the progression of CS. In other words, RUNX2 was involved in the cancer spreading. Having identified RUNX2 as a possible drug target, a drug (CADD522) was developed that would block its activity.  

Testing CADD522 in the laboratory

Now that a drug had been developed, the next step was to see the effect blocking RUNX2 had on cancer cells. CADD522 was tested in three types of bone cancer: CS, Ewing sarcoma (ES) and OS. The drug successfully reduced cell division in the CS and OS cells. The drug had a bimodal effect on ES cells. This means it caused an increase in cancer cells at lower doses, but prevented cell division at higher doses.

These initial results were promising. However, there is only so much that can be gleaned from looking at cells in a dish. Therefore, the research team moved on to look at CADD522 in OS and ES mouse models (a similar CS model has not been developed yet). CADD522 reduced the size of the tumours and increased the overall survival in the animal models.

Additionally, the tumours and surrounding bone were examined using a mini CT scan. Often bone cancer causes changes in the bone structure. However, CADD522 seemed to reduce these changes in the OS animal model. It also had no apparent harmful side effects.

What is next for CADD522

These initial results suggest that CADD522 can improve survival in bone cancers. However, this has only been tested in a laboratory setting. For this drug to enter clinical trials it must go under further investigation including toxicology assessments to see if it would be safe. This normally takes a few years. The hope is that in the future this drug may offer a new treatment for bone cancer patients and have fewer side effects than chemotherapy.

Read the full paper.