Chemotherapy is a powerful weapon against cancer, but the complexity of the cancer means it doesn’t always get the desired results, according tomedia. Scientists at the Salk Institute have been studying some of the cellular processes behind these escapisms, and have recently discovered a new mechanism that could pave the way for chemotherapy to gain the upper hand.
The work was carried out at the Salk Institute’s Molecular and Cell Biology Laboratory, where medical scientists led by Gerry Shadel set out to study the possible role of mitochondria in the effectiveness of chemotherapy.
Mitochondria are known to be the source of energy for most cells, but scientists have found that it can also serve as an early warning sign. Although most of the DNA people carry are wrapped in the nucleus, mitochondria are wrapped in their own group of DNA, called mitochondrial DNA.
When cells are stressed or attacked by viruses or chemicals such as chemotherapy drugs, mitochondrial dna is released and an immune response is activated to respond to the threat. When this happens, a group of genes called interferon-induced genes (ISGs) begin to work.
These ISGs act as a protection for DNA in the nucleus of the cell. Unfortunately, however, it acts as protective when it comes to chemotherapy drugs that target DNA in cancer cells. The team observed that this process also played a role in cancerous cancer cells in culture, and in mice, the higher the LEVEL of ISG, the stronger the resistance to the chemotherapy drug dosiliacin.
In this way, the researchers say, mitochondria are like “canaries in a coal mine” and are early warning of attacks on cells. But when this mtDNA release is triggered by amycin (anti-tumor drug), it produces an unexpected nuclear DNA protection effect, which is intended to attack nuclear DNA. Now with this new understanding, there is a new way of possible intervention.
“It tells me that if you can prevent mitochondrial DNA from being damaged or released during cancer treatment, then you may be able to prevent this form of chemotherapy resistance,” Shadel said.
Shadel and his colleagues are working on follow-up studies to better understand these processes.