The clues were always there.
Searing pain is often the first hint of pancreatic cancer.
Mood and depression swings often accompany a cancer diagnosis ‒ and not just because patients are facing their own mortality.
And when surgeons like Ed Steger's slice out tumors, they often find nerves running through the middle or crisscrossed through clumps of cancerous cells.
It's only in recent years, however, that a small number of researchers have begun to explore the role the nervous system plays in many types of cancers.
These researchers believe understanding the interplay between tumors and nerves will be essential in winning the war on cancer.
"It's a pillar of oncology that we're only now beginning to recognize," said Michelle Monje, a neuroscientist and neuro-oncologist at Stanford University, who published a related study earlier this month in the journal "Nature." "Every cancer that's been examined has shown evidence of a key role for the nervous system."
Treatments might already exist
Nerves are the cables that carry electrical impulses between the brain and the rest of the body, enabling sensations like cold, heat and pain, emotions, and even the timing of heart rate.
"So it just makes sense that the nervous system also controls the cancers that unfortunately develop in many of us," said Dr. Moran Amit, a cancer biologist and head and neck surgeon at the M.D. Anderson Cancer Center in Houston.
Without nerves, tissues can't receive signals, they can't grow and they atrophy. That's why researchers think depriving tumors of nerves may help kill cancerous cells.
Beta blockers ‒ which are typically used to treat high blood pressure, but which work by reducing nerve activity ‒ have been shown to help patients with breast and colon cancer.
People who take medications that alter the nervous system, like anti-depressants and mood stabilizers, appear to develop fewer tumors.
And epilepsy drugs that tamp down nerve cell activity in the brain may also help brain cancer patients when used in combination with other therapies, said Monje, who hopes to start testing these drugs in cancer patients in the coming months.
People shouldn't try these approaches on themselves, Monje warned, because in some tumor types, turning down the nervous system could actually amp up cancer growth.
Regardless, she and others think more research in this area could lead to dramatic improvements in care.
"The idea that you could get better results in cancer by turning to the drugs that modulate the nervous system. …Wow," said Dr. Eric Topol, founder and director of the Scripps Research Translational Institute in California. "This is a sleeping giant."
A full but limited life
Ed Steger knows all too well how important nerves are in treating tumors.
When he had a walnut-sized tumor carved out of the base of his tongue in 2006, a key nerve was necessarily taken with it.
The 12-hour surgery was life-saving but left him with problems speaking and swallowing which were compounded by radiation treatment.
"I've been on a liquid diet for over a decade," said Steger, now 71, who speaks slowly and with difficulty.
Chemotherapy left him with some nerve damage in his toes that affects his balance and parts of his face still feel numb from treatments that ended in 2007.
Still, the Houston resident has been cancer-free for a decade and is grateful to his doctors at the University of Texas MD Anderson Cancer Center for allowing him to lead a "very full life."
The retired program manager has been able to watch his daughter grow into adulthood and to volunteer as a patient advocate.
"There is life after treatment," he said.
"He's a living example of why this (work) is so important," Amit said.
Tumors and nerves are intertwined
The more Monje has looked for a connection between cancer and the nervous system, the more she's found.
Tumor cells often travel along nerve cells to other parts of the body, using them almost like highways to reach distant places, she said. But tumors also build those highways themselves, releasing chemicals that stimulate the growth of nerves.
For some brain cancer patients whose tumors sit in the part of the brain responsible for language, simply talking can spur the cancer to grow.
And she's shown that in extremely lethal brain tumors called glioblastomas and DIPG, the cancer cells form electrical connections with brain cells.
"The tumor is affecting the brain and the brain is affecting the tumor," Monje said of all these examples.
Nerves are also an integral part of most cancer's early development and progression, said Dr. Timothy Wang, a gastroenterologist and cancer specialist at the Herbert Irving Comprehensive Cancer Center at Columbia University.
For cancers to grow, they need signals from nerves, he said.
"We don't know about what the tumor is saying to the nerves and where that message goes," Wang said. But "nervous (system) signals are a two-way street. In addition to receiving signals from nerves, cancer cells are sending signals and that also plays a role in its overall strategy towards growth."
The challenge over the next five to 10 years, Amit said, is to figure out precisely what's being communicated between the tumor and the nervous system and interrupt those conversations to help the patient. "They speak with each other. We just haven't figured out the language."
Monje said she doesn't expect breaking up that cross-talk on its own will be sufficient to combat cancer. But she thinks such disruption could be extremely effective in combination with therapies designed to kill tumor cells and those that turn the immune system against cancer.
Leaving cancer patients better off
A better understanding of the connection between cancer and nerves should also lead to better pain management for patients, said Jami Saloman, a neurobiologist at the Pittsburgh Center for Pain Research.
Pain manifests differently in different types of cancers.
For pancreatic cancer, pain is often the first symptom of the disease, she said. "If we get rid of the nerves that sense pain," she wonders, "Can we improve the quality of life of patients while they're undergoing treatment?"
When researchers killed nerves that sense pain in animals with pancreatic cancer, their tumors grew more slowly.
It's possible that killing the pain-sensing nerves early in a person's disease could have the double benefit of reducing a person's suffering while also slowing the progression, Saloman said, although that has yet to be proven.
Reducing stress on the nervous system slows tumor growth
Studies show that people taking medications for mood disorders, depression, stress or anxiety have a lower incidence of cancers, Saloman said.
It may be that by reducing the stress their cells are under, these drugs improve people's ability to fight off tumors, she said. Animal studies have found that even reducing an animal's stress by keeping its environment warm slows the spread of its tumors.
That may explain one way in which beta blockers slow cancer growth, said Erica Sloan, a professor of drug discovery biology at Monash University in Australia.
Sloan led a study published earlier this year showing that combining beta blockers with chemotherapy reduced the spread of an aggressive form of breast cancer in mice and human tissue samples. The study found beta blockers reduced the stress caused by chemo, allowing the body to respond better to the treatment.
It's hard to quantify, but Sloan believes any kind of stress-relieving activity ‒ including her own favorite, yoga ‒ can be a useful part of cancer treatment by helping to reduce the stress on a patient's nervous system. "Whatever brings you joy," she said, will reduce stress and support patients in their journey through cancer treatment.
Far more research is needed into the connection between the nervous system and cancer, Sloan and others said, to make sure doctors can provide the most effective treatments.
"It's not enough to say '(this) affects cancer,'" she said. "It's important to be doing very rigorous, mechanistic science" to figure out what's really going on.
Contact Karen Weintraub at email@example.com.
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This article originally appeared on USA TODAY: The nervous system could be the key to beating many types of cancer