Seeing her uncle fight cancer more than two decades ago steered Humsa Venkatesh’s course towards studying cancer biology. When The Scientist spoke to her in 2022, Venkatesh had just established her lab at Harvard University.
Her research focused on the nervous system and how neural activity influenced brain cancer growth, as well as studying how malignant tumors remodel the surrounding nerves to promote their own progression. “When my uncle got diagnosed...I want[ed] to do something that’s going to change how we treat cancer,” Venkatesh told The Scientist in 2022.
For The Scientist’s 40th anniversary, we reached out to Venkatesh again to see what direction her work has taken over the last four years. While her initial research focused on gliomas—tumors derived from glial cells that support neurons in the central nervous system (CNS)—the scope of her research has expanded to investigating the reciprocal interaction between the nervous system and multiple types of cancer.
Uncovering Cancer’s Neural Connections
Tumor cells are known to integrate cues from their microenvironment to grow and spread.1 While other scientists had studied how glial cells and blood vessels promote brain tumor growth, Venkatesh and her colleagues focused their attention on the role of the nervous system in these cancers.2
Early in her research, Venkatesh found that electrochemical communication between neurons and tumor cells drove overall cancer growth, revealing a previously unrecognized property of the nervous system in cancers. She also helped uncover a molecule produced by neurons that drives gliomas, leading to the testing of its inhibitor in a clinical trial.3 Over time, she recognized that these findings could also have implications for cancers outside the CNS.
“The exciting part of cancer neuroscience is that the more and more we look, the more and more we find that this is such a broadly applicable topic,” said Venkatesh. “Almost every cancer that we look at has some influence from the nerves.”
Indeed, other researchers had already found that peripheral nerves, which are outside the CNS, innervate prostate, gastrointestinal, and breast cancers to drive their growth.4-6 However, the extent to which the nervous system regulated lung cancers, which are known to metastasize to the brain, remained relatively unstudied.
Bridging this gap, Venkatesh and her team found an essential role of the vagus nerve—which connects the brain to various organs—in promoting primary tumor development in the lung.7 They also found that lung cancer cells that metastasized to the brain formed synaptic connections with neurons, supporting tumor growth.
Venkatesh admitted that she was unsure how the story would evolve when she first started working on non-glial cell-derived tumors. “Were they really going to have that capacity and ability to integrate these neural inputs if they weren't derived from the brain?” Venkatesh said. “But indeed, we do see such dramatic plasticity of these cells in response to activity and almost every malignancy we check seems to have this ability to respond.”
Toward the Next Generation of Treatments
While their work has primarily focused on lung cancers, Venkatesh and her team also investigate the connection between the nervous system and melanomas and breast cancers. She said, “We now have some really exciting stories involving the brain-body connection and looking at how tumors in the periphery can actually interact with and integrate with the peripheral nervous system, which then communicates [with] the CNS.”
One of their ongoing projects also involves studying gliomas as a brain-wide disease rather than a local malignancy and investigating whether the cancer has any effect on cognition and behavior. “It's a really fascinating new area of work.”
Looking back, Venkatesh believes that one of her proudest accomplishments has been mentoring young scientists in the lab. “Not only do you get to do all of the science that you're so excited about, but you genuinely get to train the next generation and help them come into their own as scientists,” she said.
She also noted that advancements in technologies such as spatial proteomics and transcriptomics have enabled her and her team to explore relatively unknown frontiers such as looking at tumor-nerve interactions at both single cell and subcellular resolutions. “That’s really going to help us…exactly understand these interactions between various distinct cell types and tissue types,” Venkatesh noted.
With time, she hopes that she and her team can translate their findings to the clinic. “We're doing this ultimately to get this to the patients and to make a meaningful impact in how we treat and view this disease,” she said. “Our goal is to be able to help develop some more specific therapies that target malignant neural-tumor interactions in a way that might be slightly more effective than what we have now.”
And while research in the cancer neuroscience field has revealed that nerves play an integral role in tumor initiation, progression, and metastasis, “Lots of work [needs] to be done,” she said.
- Venkatesh HS. Targeting electrochemical communication between neurons and cancer. Sci Transl Med. 2023;15(706):eadi5170.
- Quail DF, Joyce JA. The microenvironmental landscape of brain tumors. Cancer Cell. 2017;31(3):326-341.
- Venkatesh HS, et al. Targeting neuronal activity-regulated neuroligin-3 dependency in high-grade glioma. Nature. 2017;549(7673):533-537.
- Magnon C, et al. Autonomic nerve development contributes to prostate cancer progression. Science. 2013;341(6142):1236361.
- Hayakawa Y, et al. Nerve growth factor promotes gastric tumorigenesis through aberrant cholinergic signaling. Cancer Cell. 2017;31(1):21-34.
- Sloan EK, et al. The sympathetic nervous system induces a metastatic switch in primary breast cancer. Cancer Res. 2010;70(18):7042-7052.
- Savchuk S, et al. Neuronal activity-dependent mechanisms of small cell lung cancer pathogenesis. Nature. 2025;646(8087):1232-1242.
