Tumor Acidosis Enhances Survival and Growth of Pancreatic Cancer Cells, New Research Finds

Research from the German Cancer Research Center (DKFZ) and the Institute of Molecular Pathology (IMP) in Vienna has shed light on how the acidic environment within tumors, known as acidosis, significantly influences the energy metabolism and survival strategies of pancreatic cancer cells. Tumors are often characterized by hostile conditions, including oxygen deprivation, limited nutrients, and the buildup of harmful metabolites, leading to a phenomenon called acidosis due to increased metabolic activity and poor blood flow.

In a groundbreaking study, scientists employed CRISPR-Cas9 gene editing to systematically deactivate individual genes in pancreatic cancer cells, observing how these changes affected tumor cell viability under stress. These experiments, initially conducted in cell cultures and then in mouse models, revealed that the tumor environment's acidity does more than just result from tumor activity—it actively controls how cancer cells adapt and sustain themselves.

A key discovery was that acidosis causes profound alterations in the mitochondria, the cell’s energy producers. Under acidic conditions, mitochondria fuse into extensive networks, becoming more efficient at generating energy. This process is largely due to the inhibition of the ERK signaling pathway, which normally promotes mitochondrial fragmentation. When mitochondria fuse, cancer cells gain increased metabolic flexibility, enabling them to utilize various nutrients more effectively and to grow despite adverse conditions.

Furthermore, acidosis triggers a metabolic shift from glycolysis, the process of sugar-based energy production, to mitochondrial respiration, which is more efficient. This shift is crucial for cancer cell survival in nutrient-scarce tumor environments. Researchers found that interfering with mitochondrial fusion slowed the growth of cancer cells in acidic conditions, highlighting potential therapeutic targets.

Dr. Johannes Zuber explained that acidosis acts as a metabolic switch, helping tumors optimize their energy supply and promoting their growth and survival. These findings suggest that targeting tumor acidity and associated mitochondrial changes could open new avenues for cancer therapy, aiming to disrupt the energy metabolism of tumors and inhibit their progression.

Published in the journal Science, this study emphasizes that acidosis is not merely a by-product of tumor activity but a central factor in tumor energy regulation, offering promising prospects for future treatments that focus on tumor metabolism.