Unboxing Cancer News, September 2026: Sugar and Cancer Risk, Psilocybin’s Chemotherapy Relief, and More

The autumn winds may blow chilly and cold, but they’ve carried with them a month of fascinating developments from the wide world of cancer research.

As you cozy up by the fire and pour a hot beverage, why not take in the second edition of Unboxing Cancer News? We have a piping-hot kettleful of stories this month, including insight into why some never-smokers may develop lung cancer; the effects of early-life sugar exposure on cancer risk; a strategy for chemotherapy pain prevention derived from psilocybin mushrooms, of all things; and more.

Magic Mushroom Trips Chemotherapy’s Pain Circuit

What a long, strange history psilocybin’s had—from disrupting the breakfasts of unsuspecting English families to undergoing clinical trials for post-traumatic stress disorder (PTSD) and smoking cessation. But a new study from Science shows yet another possible application for the freaky fungi: relieving pain from some cancer treatments.

Chemotherapy regimens that use platinum or taxanes to treat cancer frequently cause a condition known as chemotherapy-induced peripheral neuropathy (CIPN), a cluster of nerve-damage symptoms that includes numbness, sensory impairment, unpleasantly heightened sensitivity to temperature, and straightforward pain. The toll that CIPN takes on some patients can even lead to chemotherapy discontinuation, and though treatments exist that somewhat attenuate it, preventive measures to preempt CIPN have not hitherto existed.

Enter the Psilocybe genus: the colloquially “magic” mushrooms that contain the serotonergic hallucinogen psilocybin. But psilocybin is not just an experiential enhancement for Burning Man—it is also a potent activator of serotonin 2A.

Serotonin 2A receptors, the authors of the Science study reasoned, could bind to psilocybin and activate their known pro-plasticity and mitochondria-regulating effects—mechanisms that could, in turn, confer protective effects on the nerves normally damaged by chemotherapy.

In mice, one dose of psilocybin reduced the post-chemotherapy pain, and two doses eliminated it altogether. On a molecular level, they found that the psilocybin treatment activated a signaling pathway (TrkB-Akt-PAK5) that preserves mitochondrial transport along nerve axons, which chemotherapy otherwise disrupts. Because the mitochondrial transport remained intact, chemotherapy did not lead to a deprivation of energy in the cells’ axonal regions, thus preventing damage to the nerves and, ultimately, pain.

Although the study was limited to mice, it wouldn’t be the first time that psilocybin was used in a cancer setting; an ongoing clinical trial is testing whether the hallucinogen can help treat depression and anxiety in patients with advanced cancer.

Ultimately, however, psilocybin was merely a means to an end for discovering the pain prevention mechanism. The researchers found that a comparable, nonhallucinatory agonist of serotonin 2A, tabernanthalog, was just as effective in preventing CIPN in chemotherapy-treated mice, and they concluded that these prophylactic effects against CIPN warranted further clinical investigation.

Ensuring Cancer Won’t Get the Last Word: Saving the Voice Box

For patients with locally advanced head and neck squamous cell carcinoma (HNSCC), treatment can be extensive and have negative effects on quality of life.

One option includes radical surgery—an extensive surgery to remove the tumor and all surrounding tissue—but this procedure often results in organ dysfunction, such as difficulties with speaking and eating, as well as facial disfigurement. This approach is also associated with high rates of recurrence and metastasis.

Fortunately, advances in immunotherapy regimens for locally advanced HNSCC has led to greater tumor shrinkage and improved overall survival when immunochemotherapy (ICT)—which combines chemotherapy with immunotherapy—was given before surgery. Given these positive results, a new study in Clinical Cancer Research asked if this strategy could allow for less extensive surgery to help maintain positive functional outcomes.

To test this, researchers conducted a clinical trial that treated 52 patients with locally advanced resectable HNSCC with three cycles of ICT. Tumor response was monitored by imaging during ICT treatment. Patients who had greater than or equal to 50% tumor regression were eligible to undergo less extensive, reduced-volume surgery to remove residual tumor while minimally affecting nearby structures and organs; and those who had less than 50% tumor regression received standard-volume surgery.

At two years, 90% of patients who received reduced-volume surgical treatment were still alive and had not experienced disease recurrence or metastasis. Notably, this approach maintained laryngeal function in 100% of patients with laryngeal or hypopharyngeal cancers, supporting a primary goal of organ preservation.

In contrast, patients who underwent standard-volume surgery had a two-year disease-free survival rate of only 20%. One of three patients who had laryngeal or hypopharyngeal surgery experienced complete loss of laryngeal function.

The study further revealed that the higher levels of PD-L1, a protein that helps cancer cells evade the immune system, were positively correlated with response rate to ICT, indicating that PD-L1 expression may serve as a biomarker for predicting response to ICT.

Together, the results of the study provide a strong rationale to further investigate whether surgery may be individually tailored based on tumor response to ICT.

Not-so-sweet Connection Between Sugar and Cancer

Sorry for those with a sweet tooth, but there is no sugarcoating the results from our next study published in the Proceedings of the National Academy of Sciences: Less sugar in early childhood may mean a lower risk of cancer later in life. But before we get into the granular details of the study, we first need to unwrap a bit of history. During World War II, the United Kingdom started to ration individual sugar intake to about 40 grams per day for adults and 15 grams for children. When this policy was lifted in 1953, average sugar intake nearly doubled.

This sudden change from sugar rationing to sugar rush has allowed researchers to examine the potential long-term effects of sweet treats on a variety of health conditions, with this latest study focused on cancer. The researchers analyzed data from 64,761 UK Biobank participants born between 1951 and 1956 to ensure they captured information for individuals born well within the rationing period until a few years after. Specifically, they looked at the period from conception to a person’s second birthday since this is a critical period of the body’s development.

They found that people who experienced longer durations of sugar rationing during that period of development had lower incidence rates of five cancer types: liver/intrahepatic bile duct (69%), prostate (52%), lung (41%), rectal (40%), and breast (36%). The researchers noted this was a dose-dependent relationship and that these changes only started to appear decades later following sugar rationing’s bitter end.

The researchers also uncovered that while sugar highs may be fleeting, the behavioral and biological effects may be everlasting (so Willy Wonka may have been onto something). People who experienced sugar rationing in their early life continued to consume less sugar five decades later. Further, these individuals also had healthier, more diverse diets and consumed less food overall. Less sugar in early life may also help people age slower—biologically speaking. While chronological age measures how long one has been alive, biological age measures the condition of one’s cells, tissues, and organs. Those exposed to longer periods of sugar rationing were found to be biologically aging about 2.2 years slower.

For a bit of sweet relief, the researchers say this doesn’t necessarily mean children should never eat sugar, but to at least keep in mind sugar’s potential impact on the body during early childhood development.

Trekking the Appalachian Trail to the Origin of Never-smokers’ Lung Cancer

Smoking is the leading risk factor for lung cancer, but not everyone who develops the disease has a history of smoking. An estimated 15% to 20% of lung cancer patients have never smoked. Understanding why lung cancer develops in never-smokers remains an important area of research.

One potential clue emerged about 20 years ago when researchers reported a family in which several members had non-small cell lung cancer and carried an inherited mutation in epidermal growth factor receptor, or EGFR, known as T790M. EGFR is a protein involved in signaling pathways that regulate cell growth. T790M is particularly well known because it can arise in lung tumors during treatment and drive resistance to EGFR-targeted drugs. Mutations in the EGFR gene are important targets for several lung cancer therapies.

The finding provided early evidence that a mutation well known for its role in lung cancer treatment resistance could also be associated with inherited susceptibility to the disease, but it was so rare that further conclusions were limited.

Now, a new study published in Science has examined the connection on a much larger scale. The team analyzed genetic and health data from more than 3.3 million people using direct-to-consumer genetic testing data from 23andMe to investigate inheritable genetic risk factors of cancer.

The researchers focused on people who carry T790M in their germline, meaning the mutation is inherited at birth. They compared people with lung cancer to those without the disease and asked if EGFR T790M was more common among those who developed lung cancer.

Carriers of the variant had a 25-fold increased risk of lung cancer. People who never smoked and had the mutation were more than 60 times more likely to develop lung cancer than noncarriers. Notably, EGFR T790M was not associated with an increased risk of cancer in any other organ.

For those interested in history, the authors found that the mutation was more common in certain parts of the Southeastern United States and were able to trace the ancestral lineage to British and Irish groups that settled in Southern Appalachia about 200 to 225 years ago.

While the researchers are not yet sure how this mutation increases the risk of lung cancer or why it is tissue specific, the findings could have important implications for identifying people who may benefit from early detection and treatment strategies.