Chemo-brain IS real: How cancer treatment causes mental fog

Chemo-brain IS real: Scientists discover how cancer treatments damage white matter to cause mental fog

  • More than half of cancer patients treated with chemo experience brain fog 
  • ‘Chemo-brain’ is a recognized phenomenon, but poorly understood
  • Stanford University researchers found that chemo affects three types of cells in the white matter 
  • They also discovered that a drug that may block and reverse these effects 

Scientists have finally begun to work out what exactly ‘chemo-brain’ is – and may have found a way to reverse the brain fog cancer treatment cause, a new study reveals. 

More than half of patients that receive chemotherapy report experiencing a cognitive fog for months and sometimes years after undergoing the intensive cancer treatment, but doctors haven’t really understood what causes this. 

A team of Stanford University scientists, however, have identified chemo’s effects on three different types of brain cells. 

They think that chemo causes a sort of arrested development for some brain cells and blocks the activity of cells that help ensure our brain cells are well-fed with nutrients because the drug triggers an overly-active immune response. 

In their experiments on mice, a drug to quell those immune cells helped to reverse chemo’s cognitive effects, giving the team hope that a treatment could be on the horizon.  

More than half of cancer patients who undergo chemotherapy experience ‘brain-fog.’ A new study reveals how the drug affects three types of brain cells – and a potential way to reverse it

The advent of chemotherapy was a revolution in the treatment of cancer.

Around the time of World War II, the US military’s tests of mustard gas led to the discovery that compound based on mustard gas could combat some cancers. 

Soon thereafter, the predecessor to the now commonly-used methotrexate was discovered. 

Tumors grow when a DNA mutation allows cells to divide and multiply out of control. But methotrexate’s predecessor blocked that DNA from replicating, so it blocked cancer growth, too. 

Chemo’s roots in poisons and warfare are telling. Any chemotherapy is toxic to us – it’s just most toxic to carcinogenic cells.   

And our body responds accordingly. chemo often makes patients nauseous, unable to eat, makes them achy and tired and makes their hair fall out. 

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Most worryingly to many cancer patients, chemo often comes with a decline in cognitive function that can last far longer than the treatments – or even the cancers, in some cases – themselves do. 

Chemo-brain was once dismissed as a wive’s tale. 

Even the world-renowned Mayo Clinic still calls the term ‘misleading’ and says that it is ‘unlikely that chemotherapy is the sole cause of concentration and memory problems in cancer survivors. 

We are at last beginning to understand what role it does play, however. 

The Stanford researchers focused on the neuron-supporting brain cells in the white matter. 

Three particular types seemed implicated in chem-brain: oligodendrocytes, astrocytes and microglia. 

Oligondendrocytes produce myelin, the coating that protects neurons. If these sheaths are damaged incomplete or missing, signals sent between brain cells are liable to interference. Like a radio, the signals might not come through clearly – or at all. 

Astrocytes lay important supporting roles for neurons, making sure that they are running smoothly and getting sufficient nutrition. 

And microglia are the brain’s own personal immune system. 

The researchers gave some mice with cancer chemotherapy, and left the others untreated.   

In the brains of those who had had chemotherapy, the myelin-producing cells never reached maturity, so they couldn’t produce sufficient myelin to protect the neurons. 

As a result, the mice moved more slowly, and had a harder time recalling elements of an environment that should  have been familiar to them. 

Even when they were injected with cells that would become oligondendrocytes from healthy mice, the cells got stuck in a state of arrested development in the chemo-treated mice’s brains, suggesting it was something about the toxicity of the brain environment that was interfering with this process. 

On the other hand, chemo seemed to supercharge the brain’s immune cells. The microglia were ‘persistently activated’ for at least six months after chemo was administered. 

They were on the defensive, behaving as if there was an infection or other pathogen to fight off, which likely meant prioritizing defensive action over other functions like nutrition. 

Indeed, the overactivity in the microglia interfered with the astrocytes, and the neurons struggled to get enough nutrition, which could be an additional cause of brain-fog. 

Remarkably, the Stanford researchers discovered that they could use a drug that attacked the microglia to restore the balance between them and the nutrient-feeding cells – reversing the cognitive effects of the chemo. 

‘The biology of this disease really underscores how important intercellular crosstalk is,’ lead study author and Stanford neurologist Dr Michelle Monje said. 

‘In addition to existing symptomatic therapies – which many patients don’t know about – we are now homing in on potential interventions to promote normalization of the disorders induced by cancer drugs. 

‘There’s real hope that we can intervene, induce regeneration and prevent damage in the brain.’     

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Pancreatic cancer death rates rising across Europe, report reveals

Pancreatic cancer death rates in the European Union (EU) have increased by 5% between 1990 and 2016, a report launched today reveals. This is the highest increase in any of the EU’s top five cancer killers which, as well as pancreatic cancer, includes lung, colorectal, breast and prostate cancer.

‘Pancreatic Cancer Across Europe’, published by United European Gastroenterology (UEG) to coincide with World Pancreatic Cancer Day, examines the past and current state of pancreatic cancer care and treatment, as well as the future prospects, such as targeting the microbiome, for improving the prognosis for patients. Whilst lung, breast and colorectal cancer have seen significant reductions in death rates since 1990, deaths from pancreatic cancer continue to rise. Experts also believe that pancreatic cancer has now overtaken breast cancer as the third leading cause of death from cancer in the EU.

Pancreatic cancer has the lowest survival of all cancers in Europe. Responsible for over 95,000 EU deaths every year, the median survival time at the point of diagnosis is just 4.6 months, with patients losing 98% of their healthy life expectancy5. Often referred to as ‘the silent killer’, symptoms can be hard to identify, thus making it difficult to diagnose the disease early which is essential for life-saving surgery.

Despite the rise in death rates and dreadfully low survival rates, pancreatic cancer receives less than 2% of all cancer research funding in Europe. Markus Peck, UEG expert, explains, “If we are to take a stand against the continent’s deadliest cancer, we must address the insufficient research funding; that is where the European Union can lead the way. Whilst medical and scientific innovations have positively changed the prospects for many cancer patients, those diagnosed with pancreatic cancer have not been blessed with much clinically meaningful progress. To deliver earlier diagnoses and improved treatments we need to engage now in more basic as well as applied research to see real progress for our patients in the years to come.”

Microbiome—the key to turning the tide?

After forty years of limited progress in pancreatic cancer research, experts claim that new treatment options could finally be on the horizon as researchers investigate how changing the pancreas’ microbiome may help to slow tumour growth and enable the body to develop its own ‘defence mechanism’. The microbial population of a cancerous pancreas has been found to be approximately 1,000 times larger than that of a non-cancerous pancreas and research has shown that removing bacteria from the gut and pancreas slowed cancer growth and ‘reprogrammed’ immune cells to react against cancer cells.

This development could lead to significant changes in clinical practice as removing bacterial species could improve the efficacy of chemotherapy or immunotherapy, offering hope that clinicians will finally be able to slow tumour growth, alter metastatic behaviour and ultimately change the disease’s progression.

Professor Thomas Seufferlein, pancreatic cancer expert, comments, “Research looking at the impact of the microbiome on pancreatic cancer is a particularly exciting new area, as the pancreas was previously thought of as a sterile organ. Such research will also improve our understanding of the microenvironment in a metastatic setting and how the tumour responds to its environment. This will inform the metastatic behaviour and ultimately alter disease progression.”

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