Canadian researchers have demonstrated the existence of an enzyme called CAIX, which is essential for the survival of cancer cells in solid tumours. Its inhibition could help prevent the growth and spread of tumors.
- To progress and multiply despite the lack of oxygen in their environment, cancerous solid tumors need to release an enzyme called CAIX.
- By inhibiting their ability to release the enzyme, the researchers found that this caused the death of cancer cells and therefore stopped their growth.
Are scientists on the verge of finding a new therapeutic route against so-called “solid” tumor cancers?
This is suggested by new work from the University of British Columbia School of Medicine and BC Cancer Research published in the journal Science Advances. While solid cancerous tumors now represent the majority of cancers, its authors explain that they have discovered their “Achilles’ heel”: an enzyme on which they depend to adapt and survive when oxygen levels are low.
Researchers from the University of British Columbia School of Medicine and the BC Cancer Research Institute have discovered a weakness in a key enzyme that cancer cells in solid tumors depend on to adapt and survive when low oxygen levels are weak. Its inhibition could therefore allow the development of new treatment strategies to limit the progression of solid cancerous tumours.
The key role of CAIX in tumor development
To grow and multiply, solid tumors depend on the blood supply to provide them with oxygen and nutrients. As tumors progress, these blood vessels are unable to deliver oxygen and nutrients to every part of the tumor, resulting in low oxygen areas around these tumors. Over time, this oxygen-poor environment leads to acid buildup inside tumor cells.
To overcome this stress, cancer cells must therefore adapt by releasing enzymes that neutralize the acidic conditions of their environment. This allows them to survive, but also to become a more aggressive form of tumor capable of spreading to other organs. One of these enzymes is called carbonic anhydrase IX (CAIX).
Because they depend on the CAIX enzyme to survive as their environment becomes depleted of oxygen, tumors have also made it their weakness. The researchers therefore wanted to see if inhibiting the enzyme could prevent tumor cells from growing.
Researchers have identified a unique compound as an inhibitor of the CAIX enzyme. Known as SLC-0111, it is being evaluated in Phase 1 clinical trials. Using a powerful tool known as a genome-wide synthetic lethal screen , they looked at the genetics of cancer cells and systematically deleted their gene that allows them to release the CAIX enzyme.
Ferroptosis as a therapeutic route
The results showed that the enzyme played a role in the process that controls a form of cell death called ferroptosis, which occurs when iron builds up and weakens tumor metabolism and cell membranes.
“We now know that the CAIX enzyme prevents cancer cells from dying due to ferroptosis. The combination of CAIX inhibitors, including SLC-0111, with compounds known to cause ferroptosis results in catastrophic cell death and debilitates tumor growth”concludes Dr. Shoukat Dedhar, who led the study.
Researchers are now working to develop drugs that can induce ferroptosis and therefore suppress the growth of solid cancerous tumours.
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