By their very nature, cancer cells have some stark differences to healthy cells – and targeting these differences could be the key to killing cancer safely. In preclinical tests, scientists from the Wistar Institute have developed a molecule that can disrupt a protein complex that’s vital to cancer cell survival, but not to that of healthy cells.
The study centers on a newly-identified interaction between two components in a cell – a protein called mitochondrial fission factor (MFF) and the voltage-dependent anion channel-1 (VDAC1). VDAC1 regulates mitochondrial cell death, and tumors appear to highjack it to keep themselves alive longer. They do this by expressing MFF in high amounts and binding the protein to VDAC1.
So the researchers set out to investigate whether they could disrupt this process to kill the cancer cells. They began by studying which bits of the MFF protein are binding to VDAC1. Then they designed a synthetic peptide that contained these same pieces, letting it also bind to VDAC1. That blocks MFF from interacting with VDAC1, triggering a mitochondrial meltdown and in turn, cell death.
In tests on cells grown in the lab, the team found that this peptide was effective at killing prostate cancer and melanoma cells, even those that were resistant to other drugs. Importantly, the treatment didn’t affect healthy cells, leading the team to believe that tumors may be more dependent on the interaction between MFF and VDAC1 than regular cells are.
Next, the team developed a new compound that mimics the peptide and can enter cells in the body. This was tested in a few different preclinical models, both in vitro and in vivo. They used mini-organs, grown from patient cells, that mimicked lung, breast and brain cancer, as well as mice that had received transplants of human prostate cancer and melanomas.
In all cases, the compound was found to effectively inhibit the cancers. In the mouse tests, the animals tolerated the treatment and showed so signs of any unwanted side effects.
“Targeting protein-protein interaction in mitochondria is a validated therapeutic strategy that has already produced clinically approved cancer treatments,” says Dario Altieri, lead author of the study. “We are hopeful that this compound will be translated into a novel anticancer therapy with potential to be effective in multiple cancer types and less prone to drug resistance.”
As promising as the study is so far, it’s important to remember that it’s still very early days. These are just preclinical trials after all, and there’s no guarantee that results will translate to the human body. And even if they do, it would still be many years before patients could be treated.
Still, it’s always fascinating to see the different types of methods scientists are exploring in the fight against cancer.
The study was published in the journal Cancer Research.
Source: Wistar Institute
