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Scientist Receives Prize for Discoveries about Neuron-Cancer Connections

2023 Wachtel prizewinner and Science editors at NIH award event
(l-r): Courtney Malo, Tom Misteli, Humsa Venkatesh, Sudip Parikh, Science Translational Medicine (STM) Associate Editor Dorothy Hallberg, STM Managing Editor Orla Smith, and STM Associate Editor Christiana Fogg | Joseph Cariz

Cancer scientist Humsa Venkatesh is the winner of the 2023 AAAS Martin and Rose Wachtel Cancer Research Award for her research casting light on the mysterious connections between neurons and the growth of cancer cells.

Venkatesh has been at the forefront of this burgeoning research field and is recognized for her discoveries that networks of neurons can integrate with and "talk" to cancer cells to fuel their growth.

Her experiments have also revealed that this crosstalk between neurons and cancers can encourage the progression of both brain tumors like gliomas and deadly cancers that originate outside of the brain such as small cell lung cancer.

"Disrupting these neuron-cancer interactions and preventing cancers from successfully subverting mechanisms of neural development and plasticity may prove transformative for these intractable diseases," Venkatesh wrote in an essay detailing her prize-winning research, published in the July 26 issue of Science Translational Medicine.

Venkatesh, an assistant professor of neurology at Brigham and Women's Hospital and Harvard Medical School, gave a presentation on her group's research on July 28 at a ceremony hosted by the U.S. National Institutes of Health.

"Dr. Venkatesh is recognized for her groundbreaking work on the reciprocal interactions between the nervous system and cancers, particularly how neural activity can facilitate tumor progression and how these circuits can be therapeutically targeted," said Courtney Malo, an associate editor at Science Translational Medicine.

Venkatesh also received an award plaque and a check for $25,000, funded by an endowment bequeathed by Martin L. Wachtel. Wachtel was a businessman who used his wealth to recognize and support the impact of researchers and clinicians in the medical community. The Wachtel award recognizes outstanding early-career investigators in the field of cancer research.

"We need the early-career investigators, as these investigators really have made many of the current opportunities in biomedical science actually possible," said Tom Misteli, director of the Center for Cancer Research at the National Institutes of Health, at a speech at the ceremony. "And that's the spirit of the Wachtel award, to highlight that and recognize those contributions."

"When I'm asked what is it that drives my optimism in the sciences in a time of multipolarity and pulling apart … it's the creativity and innovation I see in early-career investigators," added Sudip Parikh, chief executive officer of AAAS and executive publisher of the Science family of journals.

Discovering How Neurons Shape Cancer Growth

Cancers usually depend on signals from their environment to instruct and fuel their growth. Oftentimes, the sources of these signals are healthy cells and tissues close to the tumor, such as immune cells and blood vessels.

Throughout her career, Venkatesh has endeavored to understand whether and how the nervous system shapes the growth of tumors in a similar manner.

"Given that we understand a great deal about the genetic and epigenetic mechanisms that contribute to cancer progression, I have always been interested in how the tumor microenvironment additionally contributes to cancer growth," she said.

One of her major discoveries revealed how electrochemical communication between neurons and cancer cells can drive tumor growth — which Venkatesh describes as a fundamental but largely unrecognized phenomenon in the development and growth of cancer.

During her earlier research on the growth of high-grade gliomas, she utilized genetic techniques to discover that these brain tumors depend on a synaptic molecule named neuroligin-3, which is secreted by neurons. This discovery provided a foundation for a later clinical trial that targeted neuroligin-3 to slow tumor growth in children.

In her own laboratory, Venkatesh has gone on to apply her discoveries to understand how the nervous system can also influence the growth of metastatic cancers and of tumors outside of the brain.

For example, her team recently uploaded preliminary research showing that stimulating neurons from the cortex accelerated the spread of small cell lung cancer cells that had metastasized to the brain.

In these experiments, her lab found that neurons can influence small lung cancer cells directly in the lungs. They also discovered that removing the supply of nerves for small cell lung cancer tumors slowed their growth in mice.

"We discovered that the nervous system can directly communicate with tumor cells through electrical cues to instruct growth," Venkatesh said, likening the influence of the nervous system to soils providing critical nutrients for weeds to flourish.

In her future endeavors, Venkatesh said that she plans on further probing the reciprocal interactions between neurons and different cancers both inside and outside of the brain. She especially wants to pin down the influence of specific subpopulations of neurons, which could potentially inform clinical applications of her discoveries.

Many effective therapies for cancer rely on combining different types of treatments to control or shrink growing tumors. Although Venkatesh cautioned that more research is needed, she speculated that targeting the neuron-cancer connections that she's uncovered could prove fruitful if combined with existing treatments such as chemotherapy and immunotherapy.

"Our lab aims to understand if systemic dynamics between the nervous system and the tumor are coordinated in their activity to fuel cancer growth, with the goal of translating these findings into the clinic and ultimately changing the way we treat these devasting diseases," Venkatesh said.


Joseph Cariz

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