A team of Indiana University School of Medicine researchers and their collaborators have discovered a new vulnerability in prostate cancer that could lead to the development of new treatments for this deadly disease.

The study, led by Kirk Staschke and Ronald C. Wek, was published in Science Signaling.

The research team discovered a new way to target prostate tumors by starving them of amino acids. Like other tumors, prostate cancer cells need a lot of nutrients to support their rapid growth. When nutrients are depleted, a protein called GCN2 signals the cells to make more fuel for growth.

The team initially thought that shutting down GCN2 would stop the cancer from making enough fuel to survive. While inhibiting GCN2 did slow the growth of the tumor cells, it didn’t kill them. That’s when that it was not enough.

The team found that a protein called p53 was cancer’s “Plan B”. The p53, which is functionally retained in most prostate cancers—unlike in other forms of cancer—signals to restrict cell division and gather nutrients. The researchers found that prostate cancers could be effectively destroyed when they inhibited both GCN2 and p53.

Note: it also means that in men with p53 deficient tumors, the tumors can be targeted by GCN2 inhibition.

According to Staschke, this study exploits metabolic vulnerabilities unique to prostate cancer to starve it for essential nutrients and kill the tumor cells.

Reference: Cordova, R.A., et al. (2024). Coordination between the eIF2 kinase GCN2 and p53 signaling supports purine metabolism and the progression of prostate cancer. Science Signaling, 17(864), eadp1375. DOI: 10.1126/scisignal.adp1375

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