P53-deficient oral cancers recruit and reprogram nerves to fuel tumor growth

P53-deficient oral cancers recruit and reprogram nerves to fuel tumor growth

Loss of an important tumor-suppressing gene allows head and neck cancer to spin off signals to nearby nerves, changing their function and recruiting them to the tumor, where they fuel growth and cancer progression, researchers from The University of Texas MD Anderson Cancer Center report in the journal Nature today. By cracking the mechanism that launches neuronal invasion of tumors, a known marker of poor prognosis for patients, the team has uncovered possible avenues to block the process, including the use of drugs commonly used to treat blood pressure and irregular heartbeat. Tons of studies show that patients who have lots of nerves in their tumor are doing worse – recurrence rates are higher, survival is shorter. Nerve endings found in surgically removed tumors can't be easily characterized or tracked back to their source, so it's been a neglected field, a neglected hallmark of cancer." Moran Amit, M.D., Ph.D., co-first author, assistant professor of Head and Neck Surgery "When surgeons remove head and neck cancers and find a high degree of nerve invasion, post-surgical radiation sometimes is effective," said co-senior author Jeffrey Myers, M.D., Ph.D., chair of Head and Neck Surgery. "But we really haven't understood whether the tumor was growing into the nerves or the nerve growing into the tumor and what signaling drove those interactions." Co-senior author George Calin, M.D., Ph.D., professor of Experimental Therapeutics and an expert on non-coding RNAs added that the paper "puts together for the first time the mechanism of involvement of neurons in tumor generation, a new hallmark of cancer." The team found that the neurons that invade the tumor are adrenergic nerves, which are involved in stress response. These nerves' neurotransmitters – adrenaline (epinephrine) and noradrenaline (norepinephrine) – are susceptible to drugs known as alpha and beta blockers, long used to treat high blood pressure and irregular heartbeats. In the study, mice with oral cancer treated with the adrenergic blocker carvedilol had sharply lower tumor growth and cancer cell proliferation. Myers says the team is working to develop clinical trials of adrenergic blockers, most likely in combination with other drugs. "We used to think that nerves are just randomly growing into the tumor, and that's completely wrong," Amit says. Loss of p53 flips a microRNA switch to re-program neurons Damage to the p53 gene is a major characteristic of head and neck cancers. A tumor-suppressing master transcriptional gene that governs the expression of many other genes, p53 is also mutated in a variety of cancers. Related Stories



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