PNAS: The use of cells "iron death" may hopefully help develop new cancer therapies

December 4, 2020 // -- If scientists still have a 3-50 hope in studying the chaotic biology of cancer, the same characteristics that give cancer cells the advantage of growing often offer opportunities and hopes for scientists to destroy cancer cells.
, in a study published in the international journal PNAS, scientists from institutions such as memorial Sloan Kettering Cancer Center found that cancer cells may show specific metabolic changes that make them sensitive to specific types of cell death (iron death, ferroptosis).
Photo Source: National Institutes of Health Iron Death, as the name suggests, is the death of cells induced by iron; it is usually caused by oxidative stress in cells, i.e. free agents and other corrosive chemicals accumulated in cells, which are by-products of cells that use oxygen to burn energy; but for many cancer cells that require a lot of energy to grow and divide, they find a way to avoid the problem.
researcher Jiang said that genetic mutations that promote cancer cells' response to oxidative stress may make them more resistant to iron death, in other words, cancer cells may become very, very sensitive to iron death without the benefits of the mutation.
the study, researchers tested their view by ingesting a combination of drugs in mice, one that promotes cell iron death and the other that blocks the effects of mutations.
researchers studied a particular mutation that can affect a signaling path path called PI3K-AKT-mTOR, which controls cell metabolism, and mutations in that path path line are common in cancer, and seem to reflect the fact that the need for metabolism increases significantly because cancer cells multiply too quickly, and cancers that carry the path factor mutation are often one of the most difficult cancers to treat. the
study showed that tumor cells carrying these mutations would be experimentally resistant to iron-induced drugs that give cells grown in petri dishes, and cancer cells died when researchers added drugs that blocked this metabolic path pathrail to iron-death-induced drugs.
The researchers then tested whether the same effects could be observed in mouse models of breast and prostate cancer containing these mutations, and indeed, this new combination of drugs could cause near-complete tumor damage in the mouse body.
researcher Jiang points out that this is the most significant tumor degeneration I have observed in the lab, and that the mutated PI3K-AKT-mTOR signaling path path may protect cancer cells from damage by increasing the activity of a protein involved in the production of extracellular lipids, which also protect cells from oxidative stress, thus preventing cell iron death, while blocking the PI3K-AKT-mTOR path path is able to prevent lipid synthesis and make cells sensitive to iron death again.
The findings supplement a 2019 study by researchers who found that mutations carried by certain cancer cells make them sensitive to iron death, even without giving metabolic change drugs; crucially, many cancers carry genetic mutations that can be used to induce cell iron death and cause cancer cell death, which may hopefully help scientists develop new anti-cancer therapies.
researchers say that now that we have applied for the patented technology, the next step will be to continue more in-depth research to test new drug combinations in more patients' tumor samples.
() Original source: Junmei Yi, Jiajun Zhu, Jiao Wu, et al. Oncogenic activation of PI3K-AKT-mTOR signaling suppresses ferroptosis via SREBP-mediated lipogenesis, Proceedings of the National Academy of Sciences (2020). DOI:10.1073/pnas.2017152117。