By taking advantage of the genetic differences found in cancer cells, a cancer medication that has already received approval showed improved effectiveness against tumor cells in certain patient populations, as revealed by a recent study. The results indicate the possibility of creating more personalized and effective cancer treatments.
By taking advantage of the genetic differences found in cancer cells, a cancer medication that has already received approval showed improved effectiveness against tumor cells in certain patient populations. This was highlighted in a recent study from Uppsala University, published in the journal eBiomedicine. The results indicate the possibility of creating more personalized and effective cancer treatments.
The human genome consists of 46 chromosomes, where all chromosomes except the X and Y in males are present in pairs. This means that an individual with a defective gene on one chromosome often has a working version on the other. However, during the formation of tumors, cancer cells may end up with only the defective gene.
“In cancer cells, it is common for parts of chromosomes to be lost, either in large or small segments. If the defective gene variant is the one that gets retained, the cancer cells will miss the protein normally produced by this gene. This phenomenon is known as loss of heterozygosity, leading to distinct differences between cancerous cells and normal cells. Such differences can guide the development of treatments specifically aimed at cancer cells,” explains Xiaonan Zhang, a researcher at the Department of Immunology, Genetics, and Pathology, and the lead author of the study.
In this study, the researchers examined a vast array of genes and pinpointed one that lies in a DNA region frequently lost in various cancers. This gene codes for an enzyme in the liver known as CYP2D6. They subsequently tested a range of drug compounds on modified cell models to see how CYP2D6 activity affected the drug’s impact.
“We evaluated drug compounds that are either currently in clinical use or in clinical trials. Among the most promising was a drug called talazoparib, which consistently showed increased toxicity against liver cancer cells that did not have a functional CYP2D6 enzyme,” remarks Xiaonan Zhang.
Preliminary data from the researchers also indicates that talazoparib might have CYP2D6-related effects on neuroblastoma and ovarian cancer cells. Thus, they plan to further investigate other medications that target enzymes in different organs where enzyme activity levels can vary.
“We think that by using loss of heterozygosity and the natural genetic variations within cancer cells, we can discover new treatment possibilities that lead to therapies customized to each patient’s unique genetic makeup. This approach holds promise for advancing precision medicine, not only in cancer treatment but across various healthcare fields. By tailoring treatments to match patients’ specific genetic traits, we can develop more effective therapies and improve outcomes,” states Tobias Sjöblom, a professor at the Department of Immunology, Genetics, and Pathology and the study’s lead researcher.
The study was conducted in partnership with researchers from Switzerland and the Chemical Biology Consortium Sweden (CBCS).
