Because anticancer drugs are designed to kill growing cells, they also affect normal, fast-growing cells糖心传媒攂lood 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糖心传媒攁t least, it appears, in male mice.
糖心传媒淭hat was the unexpected part,糖心传媒� 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糖心传媒攁 糖心传媒渞egulated糖心传媒� 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.
糖心传媒淲e don糖心传媒檛 know why that is,糖心传媒� Fu says. 糖心传媒淏ut we have some potential leads.糖心传媒�
Fu suspects that additional genetic and molecular factors, including hormones and other cellular proteins, affect a cell糖心传媒檚 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.
糖心传媒淪o that brings up an intriguing point, that male and female cells die in different ways depending on what they are exposed to,糖心传媒� Fu says. 糖心传媒淚f you give a male and a female the same dose of chemotherapy, it could have completely different effects.糖心传媒�
Fu will continue to study the role of ALKBH7糖心传媒攏ow taking the possibility of sex-specific behaviors of the protein into account. Further research on ALKBH7 will help to determine:
- Whether there are certain cancers that arise from ALKBH7 deficiency
- And if so, are there ways to selectively re-introduce the ALKBH7 protein糖心传媒攐r other proteins that trigger cell death糖心传媒攊nto cancer cells but not in the normal cells?
In addition, in a previous study, Fu found that cells lacking ALKBH7 have a greater number of mutations after chemotherapy compared to cells with ALKBH7. 糖心传媒淭hus, we have to weigh the cost/benefit of increasing the survival rate of normal cells with the increased risk of mutation and cancer,糖心传媒� he says.
糖心传媒淏y gaining a better understanding of how cells respond to chemotherapy, we are hoping to make these therapies more targeted for certain kinds of cells, such as a cancer cells糖心传媒攁nd also, importantly, to lessen the affects they have on our normal cells,糖心传媒� Fu says.
The study is a continuation of research Fu began prior to coming to Rochester, when he was an American Cancer Society postdoctoral fellow in the lab of study co-author Leona Samson, a professor of biological engineering at MIT. Samson is an expert in how cells respond to chemotherapy. While in Samson糖心传媒檚 lab, Fu collaborated with lead author Jennifer Jordan, a postdoctoral fellow, on uncovering the role of ALKBH7 in triggering cell death after chemotherapy.
