Central OC Times

A research team led by the University of California, Irvine has identified the critical role played by the APOBEC3A and APOBEC3B enzymes in driving cancer mutations by altering DNA in tumor genomes. The findings offer new possibilities for intervention strategies in cancer treatment.

Corresponding author Rémi Buisson, UCI assistant professor of biological chemistry, emphasized the importance of understanding how cancer cells accumulate mutations that contribute to disease progression and drug resistance. Buisson stated, "Both APOBEC3A and APOBEC3B were known to generate mutations in many kinds of tumors, but until now we did not know how to identify the specific type caused by each. This finding will allow us to develop novel therapies to suppress mutation formation by directly targeting each enzyme accordingly."

The study, published in the journal Nature Communications, detailed the process by which APOBEC3A and APOBEC3B detect specific DNA structures, leading to mutations at distinct positions within the tumor genome. Graduate student Ambrocio Sanchez and postdoctoral fellow Pedro Ortega, both part of Buisson's laboratory at the UCI School of Medicine, developed a new method to characterize the DNA modified by these enzymes. They found that the two enzymes recognize different DNA sequences and structures within cancer cell genomes.

Buisson highlighted the next steps in the research, which include investigating whether mutations caused by these enzymes contribute to therapy resistance and identifying molecules that can inhibit APOBEC3A and APOBEC3B to prevent mutations. He noted that the findings could help assess patient risk before treatment and suppress tumor evolution using appropriate drug therapy.

The study involved collaboration among undergraduate and graduate students, as well as postdoctoral fellows from UCI, Harvard Medical School, the University of Southern California, the University of Texas at San Antonio, and the University of Minnesota. The research was supported by various grants and awards from institutions such as the National Institutes of Health and the Cancer Prevention and Research Institute of Texas.

The University of California, Irvine, known for its academic excellence and research achievements, continues to make strides in the field of cancer research. The findings of this study open up new avenues for developing targeted therapies in the fight against cancer.