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Touching a nerve: How neuroscience might advance our understanding of most cancers – Most cancers Analysis UK

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When supporters donate to our work, their combined generosity could lead to a new discovery that, for example, brings us closer to a new class of life-saving treatments. Or it could help fund a clinical trial testing experimental new drugs. On occasion – like those who support our researchers in Edinburgh or who jointly donated £ 100 million to build our flagship Francis Crick Institute in London – your generosity could even help usher in a whole new field of cancer research.

See the bigger picture

Researchers, including us, have long studied how the body’s immune system can be used effectively to fight cancer – with some brilliant results. However, until now, less attention has been paid to how cancer interacts with other systems in the body, such as the nervous system. Now, an emerging school of thought is calling for a more holistic view of the origins, evolution, and impact of cancer, rather than instantly zooming in on a tumor or organ. As our Chief Medical Officer Professor Charlie Swanton recently said, “It is time to focus on cancer as a systemic disease, not just a clot of rapidly dividing cells.” And cancer neuroscience might just be the next part of the equation.

Cancer Neuroscience – A Whole New World of Opportunities

As modern academic fields, neurosciences – the study of the structure and function of the nervous system – and cancer biology have coexisted for over a hundred years. Why does the role of the nervous system in cancer progression remain largely unexplored? Dr. Leanne Li, group leader at the Cancer Neuroscience Laboratory at Crick, suspects this has to do with the high barriers to entry in these areas, which make it difficult to find experts who combine the two.

Leanne, who is from Taiwan and studied in Switzerland and the United States before joining Crick, says that crossing those academic boundaries is like switching between cultures. “Every culture has a unique language and customs. The same goes for cancer biology and neuroscience, ”she explains. “Cancer is hectic and unpredictable, with mutations being one of the defining characteristics. But the nervous system is much more orderly and logical. We know that it regulates full body homeostasis in a well-coordinated and sophisticated way. “

Dr. Leanne Li

The approaches, techniques and even mentalities required to study the two areas are therefore naturally different. But by adopting these idiosyncrasies, researchers could lead us to surprising new discoveries. “If you look at the same question from different perspectives,” says Leanne, “and try to answer it by applying rules from different areas, you begin to see a whole new world of possibilities.”

What do these pioneering researchers hope to find out now? By and large, the field can be divided into two central areas of investigation, which we are delving into thanks to ongoing philanthropic support.

Repurpose the wheel

A group of cancer neuroscience researchers is interested in how cancers of the central nervous system – such as brain tumors – interact with other brain cells in order to survive and grow. One of them is Dr. Dirk Sieger, who is studying a common type of brain tumor called glioblastoma.

Dirk moved to the University of Edinburgh in 2012, where he was inspired by the world’s leading neuroscience and brain tumor experts to ask new questions about the dependence of cancer on healthy biological systems. In 2015 he received the Career Establishment Award from Cancer Research UK, with which he was able to set up his first research group in this field.

“Tumors are not reinventing the wheel,” summarizes Dirk. “They use neural mechanisms and signals that are already in place for other healthy biological processes.” One of these mechanisms involves brain-specific immune cells called microglia. These busy cells are involved in the development of the brain and receive and respond to signals from other parts of the brain. Microglia also have classic immune cell functions and intervene to repair damage, remove cell debris and attack harmful cells.

Dirk’s first results supported the theory that glioblastoma tumors were specific neural

Dr Dirk Sieger

Dr Dirk Sieger

Mechanisms for mimicking signals from a healthy brain. This misleads the microglia and puts them on unfortunate tasks to assist the tumor rather than triggering an anti-tumor response. His team is now building on this knowledge with new funds from Cancer Research UK to test their theory that microglial tumors not only help with smaller tasks, but also help them form networks with other cells. “Microglia have long, fine protrusions that they send out to probe their surroundings and make contact with neighboring cells,” he explains. “We have some indications that this contact makes the tumor more aggressive, more invasive and more resistant to therapy.”

Dirk hopes that by learning this process, his team can find a way to restore the microglia to their original function – and thereby cut off this vital artery for the tumor.

Speak the same language

But what about cancers in other parts of the body? How do cancers outside of the central nervous system, such as lung cancer, interact with nerve cells to survive and grow?

Leanne has just started her multidisciplinary group at Crick, but based on her preliminary findings, she has also come to the conclusion that other cancer cells can hijack signals from nerve cells for their own benefit.

Since these are two different cell types with seemingly minimal similarity, one might expect that nerve cells and cancer cells “speak different languages”. But Leanne found that some cancer cells adopt the language of nerve cells. While Dirk only investigated microglia that only occur in the brain, Leanne found that this was the case with nerve cells that are responsible for functions around the body. This gave rise to her current hypothesis: the body can “communicate” with a tumor via the nervous system.

“Different forces are used,” says Leanne. “There are nerve signals that try to control the tumor and others that are overtaken by the tumor and encourage its growth. If we can find out how these opposing forces work, we could tip the balance in favor of tumor regression. “

Leanne’s approach is unique in that while a handful of teams around the world study tumors outside of the central nervous system, they focus on specific types and pathways of cancer. Instead, she says, “I want to take a systematic approach to identify general rules for different types of cancer, not just for primary tumors but also for metastatic ones.” Finding such a rule would be an important turning point in our understanding of cancer development.

Cooperation spirit

Both Leanne and Dirk credit their respective institutes for creating the perfect conditions for testing their bold hypotheses. At the Crick, Leanne only needs to travel upstairs to brainstorm a neuroscience expert. And that spirit of collaboration is shared in Edinburgh. “Everyone is always open to team up to develop new ideas,” emphasizes Dirk. “You get valuable input from many different perspectives.”

It is crucial that we can offer them long-term support thanks to our sponsors – both groups are sponsored for at least six years. “It gives us the opportunity to take time for unexpected insights and to dig deeper,” says Dirk. “This often leads to new insights that can make the difference.”

While their projects are still in the early stages, Leanne and Dirk believe that they could lead to new treatments and that other existing treatments for cancer patients could be re-used as well. For example, Leanne believes that current treatments for various neurological diseases such as Parkinson’s could be repurposed in the future to redirect the misfiring nerve cells that promote the growth of cancer.

James Reynolds, a longtime Cancer Research UK supporter and one of Crick’s founding philanthropists, once told us, “The first time I visited Crick when it was a construction site, my wife and I walked through the labs and said to ourselves, ‘In cancer will be defeated in this building. ‘”With bold new approaches like cancer neuroscience, we are nearing the day when his hopes for the institute – and humanity – will come true.

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