Researchers have identified a key enzyme that cancerous tumours rely on to grow and spread within the body. Described as cancer’s “Achilles Heel”, scientists believe that targeting this enzyme stops tumour cells from growing and spreading. The findings could accelerate the development of new treatments for solid-tumour cancers.
Solid cancerous tumours rely on an available source of oxygen and nutrients from the blood supply to grow. But, as tumours grow, the blood supply doesn’t deliver enough, causing low oxygen levels inside the tumour. This oxygen becomes acid. In response, cancerous cells release a specific enzyme – identified as Carbonic Anhydrase IX (CAIX) – to neutralise this acid, enabling them to grow. This programmed response can make tumours more aggressive, in some cases encouraging them to spread to other organs.
In a new study published in Science Advances, researchers describe how they used an advanced technique known as genome-wide synthetic lethal screen to examine the genetics of cancer cells. Specifically, they explored whether neutralising CAIX and specific genes would kill cancer cells. Using the technique, researchers systematically targeted and deleted cells one by one to identify any potential candidates, with fascinating results into how CAIX functions.
The team discovered that the CAIX enzyme protects cancerous cells from ferroptosis, a process where iron accumulates and affects the cell’s metabolism. “We now know that the CAIX enzyme blocks cancer cells from dying as a result of ferroptosis,” explains Dr Shoukat Dedhar, a professor at the University of British Columbia and a senior author of the paper.
Dr Dedhar and colleagues have developed a unique compound known as SLC-0111 that can target and inhibit the CAIX enzyme. Currently the subject of Phase 1 clinical trials, pre-clinical models showed impressive potential for slowing tumour growth in breast, pancreatic and brain cancers by inducing ferroptosis. “Combining inhibitors of CAIX, including SLC-0111, with compounds known to bring about ferroptosis results in catastrophic cell death and debilitates tumor growth,” says Dr Dedhar.
The research is a fascinating insight into the cellular mechanisms of cancer and provides strong support for the potential of research into ferroptosis as a cancer cure. “Cancer cells depend on the CAIX enzyme to survive, which ultimately makes it their ‘Achilles heel,” says Dr Dedhar. “By inhibiting its activity, we can effectively stop the cells from growing.”
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You can read the full paper, Genome-wide synthetic lethal screen unveils novel CAIX-NFS1/xCT axis as a targetable vulnerability in hypoxic solid tumors, here.