- Whether there are certain cancers that arise from ALKBH7 deficiency
- And if so, are there ways to selectively re-introduce the ALKBH7 protein—or other proteins that trigger cell death—into cancer cells but not in the normal cells?
Science & Technology
Protein identified in post-chemo cell death puzzle
Because anticancer drugs are designed to kill growing cells, they also affect normal, fast-growing cells—blood cells forming in the bone marrow, for example, and digestive, reproductive, and hair follicle cells. Chemotherapy may also affect cells in vital organs, such as the heart, kidney, bladder, lungs, and nervous system.
Researchers at the University of Rochester, collaborating with colleagues at MIT, Harvard, and the University of Oslo, have identified a protein that is required for cell death after undergoing chemotherapy—at least, it appears, in male mice.
“That was the unexpected part,” says Dragony Fu, an assistant professor of biology at Rochester and corresponding author of the study, regarding the sex-specific nature of the experimental results.
The researchers used mice that were engineered to lack a protein they suspected would otherwise cause normal cells to self-destruct after exposure to chemotherapy or other stresses—a “regulated” death aimed at heading off the risk of mutation. The protein, ALKBH7, is one of several proteins that can trigger cell death in both mice and humans.
In the study, published in Cell Death & Disease, the researchers show that healthy photoreceptor cells and cerebellar granule neuron cells were significantly more likely to survive chemotherapy in mice that had been genetically engineered to lack ALKBH7, as opposed to control mice that still had ALKBH7.
But surprisingly, the improvement in brain cell survival rates occurred only in male mice, and was far more pronounced in males for photoreceptor cells as well.
“We don’t know why that is,” Fu says. “But we have some potential leads.”
Fu suspects that additional genetic and molecular factors, including hormones and other cellular proteins, affect a cell’s response to chemotherapy. For example, the XY chromosome cells found in males have different mechanisms for triggering cell death than the XX chromosome cells found in females.
“So that brings up an intriguing point, that male and female cells die in different ways depending on what they are exposed to,” Fu says. “If you give a male and a female the same dose of chemotherapy, it could have completely different effects.”
Fu will continue to study the role of ALKBH7—now taking the possibility of sex-specific behaviors of the protein into account. Further research on ALKBH7 will help to determine: