The study suggests that IMPDH2 could serve as a biomarker for predicting tumor responses to PARP1 inhibitors, which are currently used in cancer treatment, potentially improving patient outcomes.

The first study highlights that the nucleus has its own metabolic needs, indicating it is an active site for metabolic activity rather than merely a passive storage space for DNA.

Overall, these studies suggest that targeting metabolic enzymes could lead to innovative cancer therapies that disrupt both energy production and DNA repair processes, potentially improving treatment outcomes for drug-resistant cancer cells.

Researchers at the Centre for Genomic Regulation (CRG) have made a groundbreaking discovery that metabolic enzymes, traditionally associated with energy production, also play critical roles in the cell nucleus, including functions related to cell division and DNA repair.

This research is the first to demonstrate that the nucleus relies on metabolic pathways to maintain genomic integrity, challenging established perceptions of nuclear functions.

Published in two papers in Nature Communications, these findings challenge long-held views in cellular biology and suggest new therapeutic pathways for cancer treatment, particularly for aggressive tumors like triple-negative breast cancer (TNBC).

In the context of TNBC, which accounts for approximately 200,000 new cases annually worldwide, researchers found that the enzyme IMPDH2 relocates to the nucleus to assist in DNA repair, enabling cancer cells to survive despite DNA damage.

Both studies emphasize the potential of targeting metabolic vulnerabilities in cancer cells, proposing a dual approach that disrupts both energy production and DNA repair processes to enhance treatment efficacy.

Lead author Dr. Sara Sdelci describes this phenomenon of enzymes performing additional roles beyond their primary functions as 'moonlighting,' likening it to a baker who also brews beer.

Another enzyme, MTHFD2, traditionally found in mitochondria, has been shown to play an essential role in the nucleus for proper cell division, further altering our understanding of nuclear processes.

The research indicates that there may be many more metabolic enzymes with dual roles yet to be discovered, opening new avenues for scientific and medical advancements.

This discovery, published on November 12, 2024, challenges traditional views of cellular compartmentalization and suggests a more interconnected cellular function.