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Ayala paper garners Science magazine honors

By Roman Petrowski, McGovern Communications
Dr. Gustavo Ayala
Gustavo Ayala, MD

The journal Science honored Gustavo Ayala, MD, professor and Distinguished Chair in Pathology and Laboratory Medicine, as the runner up for its Scientific Breakthroughs of 2025.

The 2025 Breakthrough of the Year highlights major advances across all scientific disciplines. Published by the American Association of Advancement Science, the magazine is one of the world’s leading peer-reviewed academic journals.

Ayala received the honor for his article “Nerve-to-cancer transfer of mitochondria during cancer metastasis,” published in Nature in June 2025.

“To me, this honor means validation,” Ayala said. “I published the first paper on cancer neuroscience, the relationship between nerves and cancer, 27 years ago. It wasn’t easy, and I dedicated my career to this. I wrote my grants on this, and it wasn’t accepted for a very long time. And in the past five years, it’s just exploded, and for me it’s amazing.”

Ayala began his work in 1998 after noticing a lack of biological research on perineural invasion. He published his first paper on the symbiotic relationship that nerves and cancer cells have with each other, and how each nerve and cancer cells help grow each other.

Ten years later, Ayala pioneered a study on axonogenesis and neurogenesis, which showed that cancer actually creates its own nervous system. This led to the important discovery that cancer cannot survive if you cut its nerves.

“We did a lot of mechanistic studies, and what we found was that nerves regulate the energetic plasticity of cancer cells,” Ayala said. “The Warburg Effect, cancer cells being glycolytic, exists only in the absence of nerves. You put nerves and they become mitochondrial respiration dependent.”

The current research focuses on how breast cancer cells interact with nerve cells in the tumor microenvironment to promote tumor growth. The study found that mitochondria transfer from neurons to cancer cells, which enhances energy production and the tumor’s ability to survive under different types of stresses.

The research team utilized botulinum neurotoxin type A to block nerve signaling in a breast cancer model. This blocking showed slower tumor growth and reduced the tumor’s aggressiveness, suggesting that the nerve signals play a key role in tumor metabolism and progression.

From there, the team developed a novel, custom software tool to use alongside the genetic tool MitoTracer to track mitochondria transfer between neurons and cancer cells. In observing these models, they discovered that metastatic cancer cells with neuron-derived mitochondria metastasized at a distance, like in the brain or the lung, which showed a link between metabolic adaptation and metastatic success.

This research opens up the door for new therapeutic strategies focusing on targeting cancer cell metabolic plasticity acquired through interactions with nerve cells as opposed to only addressing cell motility.