Glioblastoma (GBM), a highly aggressive type of brain cancer, develops in the supportive tissues of the brain and spinal cord, known as glial. Accounting for about 45% of brain and central nervous system tumors, GMB has become the most common brain tumor in adults. Sadly, GBM outcomes remain dismal, with median survival around 15 months.
Given the rarity of novel approaches to treating GMB, a recent study published in Communications Biology is of utmost importance. It provides new and exciting insights into mechanisms for cancer cell killing, offering a ray of hope in the battle against this aggressive brain cancer.
Cell death can take many forms. Apoptosis, a common method of cell death, involves a series of molecular steps leading to the elimination of abnormal cells. Many cancer cells have evolved to block apoptosis, thereby improving their chances of survival. Another form of cellular death, ferroptosis, occurs when iron accumulates in a cell, resulting in the depletion of antioxidant enzymes.
The researchers performed RNA sequencing, revealing all the genes present in the cell. Through this method, they identified a tumor-suppressor protein, Par-4, that became activated during ferroptosis. The study then investigated the role of Par-4 by genetically depleting it from cells. They found that apoptosis couldn’t occur in cells lacking Par-4. Further, genetically overexpressing Par-4 in cells pushes the cells to undergo ferroptosis.
The study also revealed that Par-4-driven ferroptosis utilizes principles of autophagy, another biological process where cells break down damaged or abnormal proteins, recycling them to power cellular functions during periods of stress. This means that Par-4 not only triggers ferroptosis, but also utilizes the cell's own mechanisms, like autophagy, to carry out this process. Because cancer cells need to function under stressful conditions in order to survive, autophagic cell death can help fuel cancer cells in some situations.
These findings, which highlight the crucial role of Par-4 in ferroptosis, have the potential to inspire and motivate the development of new drugs and therapies for GBM. The study's implications are far-reaching and could significantly impact the field of cancer research.
Sources: NLC StatPearls, Commun Biol