Synthetic substance inhibits bone cancer growth
Some cancers depend on a certain protein in order to grow. Researchers have now created a substance that can block this protein in living cancer cells.
Cancer tumours can be regarded as a species of parasites that have developed an arsenal of tricks enabling them to grow in our bodies.
Each cancer has its own tricks. To have any hope of stopping the tumours from growing, we need to find a way to prevent the cancer from using its tricks. And this is where a Danish research team has now made a breakthrough.
They have created a substance, which in test tubes inhibits the growth of certain cancers, including bone cancer.
“The substance blocks a mechanism upon which 5-10 percent of all cancers are dependent. We hope that in the long run it will be possible to develop drugs based on this substance, drugs that can help seriously ill cancer patients who are difficult to treat with existing drugs or methods,” says Professor Ian David Hickson, who headed the study at Copenhagen University’s Center for Healthy Aging.
Two mechanisms lead to growth
The new substance acts on a mechanism which mainly occurs in two cancers: sarcoma and osteosarcoma. Sarcomas are rare cancers that develop in the supporting or connective tissues of the body such as muscle, bone, nerves, cartilage and blood.
Osteosarcoma is a rare, malignant bone tumour. It is one of the few cancers that begins in the bones and may spread elsewhere, usually to the lungs or other bones.
It is not a natural substance that is e.g. extracted from a plant. It’s a synthetic substance developed by the researchers in the lab as one of thousands of others whose respective ability to switch off the biological mechanism in question were tested using sophisticated technology.
The substance they are pointing to – known as ML216 – forces the cancer cells to resume the natural ageing process, which they have cleverly managed to dodge.
The age of a cell is determined by measuring the so-called telomeres, which function as tiny protective caps at the tips of our chromosomes.
Every time the cells divide, a little piece of their telomeres is chopped off, until only a tiny, indivisible piece remains. When the telomere is worn down, the cell can no longer divide and it dies.
Cancer cells forced to retreat
Ian David Hickson started working on this study while he was still working as a researcher at Oxford University.
The project was started up in close partnership with the US National Institute of Health, which is still heavily involved in the project.
Cancer cells can switch off this natural suicide process by repairing the telomeres, so they remain intact during cell division.
This reparation can be performed either by producing the ’telomerase’ enzyme, or by activating a process known as ‘alternative lengthening of telomeres’ (ALT), which is dependent upon the BLM enzyme. It’s this latter process that the ML216 substance can stop by blocking the BLM enzyme.
“In the 5-10 percent of all tumours that use the ALT mechanism to maintain the growth momentum, the BLM protein is used as a way of keeping the mechanism running,” says Hickson.
“If we use the ML216 to stop the effect of the BLM, the tumour will stop growing.”
The substance increases long-term cancer risk
The researcher points out that he and his research group are still a long way from having developed an actual drug that can be used in cancer treatment.
The discovery is merely the first step along the way and many further challenges lie ahead.
One of the weaknesses of the treatment is that it increases the patients’ risk of developing other cancers in the long term. The BLM protein is not only used by cancer cells while they’re growing;
the protein also stabilises healthy cells, which lowers the risk of these cells mutating and developing into cancer cells during division.
Disabling the BLM protein thus stops the growth of cancer cells on the one hand, while on the other hand it increases the risk of new cancer cells emerging 20 years after a completed treatment.
“Our hope is that eventually we can develop drugs that stop cancer cells the way that ML216 does, but which do not induce new cancers. But even if we’re unsuccessful, the new substance will probably help many patients here and now, as they would otherwise be dying from their disease. We hope the drug will prolong the patients’ lives significantly.”
The researchers will continue looking into this in upcoming studies with mice and rats.
Translated by: Dann Vinther
- “A Small Molecule Inhibitor of the BLM Helicase Modulates Chromosome Stability in Human Cells”, Chemistry and Biology (2013), DOI: 10.1016/j.chembiol.2012.10.016