New therapy turns cancer cells into fat to stop it from spreading

Researchers at the University of Basel in Switzerland have hijacked cancer's cellular plasticity to turn the disease against itself.

Photo credit: BEHROUZ MEHRI / AFP / Getty Images
  • In 2018, an estimated 627,000 women died from breast cancer worldwide.
  • Researchers recently discovered a drug combination that turned cancer cells into fat cells, preventing its proliferation.
  • The drug therapy could be used to halt metastasis, the leading cause of death from cancer.

It may be a family member, a friend, a coworker, or even yourself, but chances are breast cancer will invade your life at some point. According to the Center for Disease Control and Prevention, 242,476 new cases of female breast cancer were reported in 2015 alone. The disease took the lives of 41,523 women that same year. This makes breast cancer the most commonly diagnosed cancer, and the second leading cause of cancer deaths among American women.

Worldwide, cancers represent the second leading cause of death, surpassed only by heart disease. Yet despite these disheartening numbers, we are making progress in developing effective treatments against this deadly affliction.

Scientists may have given us another tool to further this progress. They've developed a new drug therapy that prevents malignant cancer growth. How? By turning cancer cells into fat.

The good kind of fat

Low magnification micrograph of a metastatic tumor [left side] in the ovary. This tumor metastasized from a tumor in the woman's breast. Photo credit: Wikimedia Commons

Metastasis is the leading cause of death from cancer, occurring when cancer cells separate from the original tumor to proliferate elsewhere. These new cancer cells travel through the bloodstream or lymphatic system. Since these bodily systems are thoroughly connected, cancer can spread to a variety of locations. Breast cancer, for example, "tends to spread to the bones, liver, lungs, chest wall, and brain."

Cancer cell plasticity — an ability that allows cancer cells to shift physiological characteristics dramatically — fosters metastasis and is responsible for cancer's resistance to treatments. To combat its resistance, researchers at the University of Basel in Switzerland decided to turn cancer's cellular plasticity against itself. They used Rosiglitazone, an anti-diabetic drug, along with MEK inhibitors in mice implanted with breast cancer cells. Their aim was to alter the cancer cells.

The drug combination hijacked the breast cancer cells during epithelial-mesenchymal transition (EMT), a process by which the cells undergo biochemical changes. EMT plays a role in many bodily functions, such as tissue repair. In unaltered cancer cells, EMT allows them to migrate away from the original tumor while maintaining their oncogenic properties.

But in cancer cells assaulted by the new drug therapy, EMT changes them into adipocytes, or fat cells. Like normal fat cells, these former breast cancer cells were both functional and post-mitotic, meaning they could no longer divide and proliferate.

While the therapy did not alter the original tumor, it did prevent new cancer cells from dividing and spreading elsewhere in the body. This repressed metastasis in the researcher's preclinical trials.

The researchers published their findings on January 14 in the journal Cancer Cell.

"In future, this innovative therapeutic approach could be used in combination with conventional chemotherapy to suppress both primary tumor growth and the formation of deadly metastases," senior study author Gerhard Christofori told Medical News Today.

Since the research used FDA-approved drugs to study the treatment's effects, the study notes, "a clinical translation may be possible."

Will we win the battle against cancer?

Members of Lebanon's Ladies of Harley hold placards as take part in an event organised by Pink Steps Lebanon to raise awareness about breast cancer on October 28, 2018. Photo credit: MAHMOUD ZAYYAT / AFP / Getty Images

This article opened with some fearful figures about cancer and its effect on people worldwide. But there's reason to hope.

While the total number of new cancer cases and deaths continues to increase, the rates of cancer diagnoses and deaths decline each year — as absolute figures don't account for rises in life expectancy, population growth, or aging populations. We've made great strides in understanding the disease and its various genetic and environmental origins. And events like Breast Cancer Awareness Month continue to educate the populace about the preventative measures available to them.

Thanks to scientists like those at the University of Basel in Switzerland, we may have more reasons to be hopeful very soon.

Yug, age 7, and Alia, age 10, both entered Let Grow's "Independence Challenge" essay contest.

Photos: Courtesy of Let Grow
Sponsored by Charles Koch Foundation
  • The coronavirus pandemic may have a silver lining: It shows how insanely resourceful kids really are.
  • Let Grow, a non-profit promoting independence as a critical part of childhood, ran an "Independence Challenge" essay contest for kids. Here are a few of the amazing essays that came in.
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Four philosophers who realized they were completely wrong about things

Philosophers like to present their works as if everything before it was wrong. Sometimes, they even say they have ended the need for more philosophy. So, what happens when somebody realizes they were mistaken?

Sartre and Wittgenstein realize they were mistaken. (Getty Images)
Culture & Religion

Sometimes philosophers are wrong and admitting that you could be wrong is a big part of being a real philosopher. While most philosophers make minor adjustments to their arguments to correct for mistakes, others make large shifts in their thinking. Here, we have four philosophers who went back on what they said earlier in often radical ways. 

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The surprise reason sleep-deprivation kills lies in the gut

New research establishes an unexpected connection.

Reactive oxygen species (ROS) accumulate in the gut of sleep-deprived fruit flies, one (left), seven (center) and ten (right) days without sleep.

Image source: Vaccaro et al, 2020/Harvard Medical School
Surprising Science
  • A study provides further confirmation that a prolonged lack of sleep can result in early mortality.
  • Surprisingly, the direct cause seems to be a buildup of Reactive Oxygen Species in the gut produced by sleeplessness.
  • When the buildup is neutralized, a normal lifespan is restored.

We don't have to tell you what it feels like when you don't get enough sleep. A night or two of that can be miserable; long-term sleeplessness is out-and-out debilitating. Though we know from personal experience that we need sleep — our cognitive, metabolic, cardiovascular, and immune functioning depend on it — a lack of it does more than just make you feel like you want to die. It can actually kill you, according to study of rats published in 1989. But why?

A new study answers that question, and in an unexpected way. It appears that the sleeplessness/death connection has nothing to do with the brain or nervous system as many have assumed — it happens in your gut. Equally amazing, the study's authors were able to reverse the ill effects with antioxidants.

The study, from researchers at Harvard Medical School (HMS), is published in the journal Cell.

An unexpected culprit

The new research examines the mechanisms at play in sleep-deprived fruit flies and in mice — long-term sleep-deprivation experiments with humans are considered ethically iffy.

What the scientists found is that death from sleep deprivation is always preceded by a buildup of Reactive Oxygen Species (ROS) in the gut. These are not, as their name implies, living organisms. ROS are reactive molecules that are part of the immune system's response to invading microbes, and recent research suggests they're paradoxically key players in normal cell signal transduction and cell cycling as well. However, having an excess of ROS leads to oxidative stress, which is linked to "macromolecular damage and is implicated in various disease states such as atherosclerosis, diabetes, cancer, neurodegeneration, and aging." To prevent this, cellular defenses typically maintain a balance between ROS production and removal.

"We took an unbiased approach and searched throughout the body for indicators of damage from sleep deprivation," says senior study author Dragana Rogulja, admitting, "We were surprised to find it was the gut that plays a key role in causing death." The accumulation occurred in both sleep-deprived fruit flies and mice.

"Even more surprising," Rogulja recalls, "we found that premature death could be prevented. Each morning, we would all gather around to look at the flies, with disbelief to be honest. What we saw is that every time we could neutralize ROS in the gut, we could rescue the flies." Fruit flies given any of 11 antioxidant compounds — including melatonin, lipoic acid and NAD — that neutralize ROS buildups remained active and lived a normal length of time in spite of sleep deprivation. (The researchers note that these antioxidants did not extend the lifespans of non-sleep deprived control subjects.)

fly with thought bubble that says "What? I'm awake!"

Image source: Tomasz Klejdysz/Shutterstock/Big Think

The experiments

The study's tests were managed by co-first authors Alexandra Vaccaro and Yosef Kaplan Dor, both research fellows at HMS.

You may wonder how you compel a fruit fly to sleep, or for that matter, how you keep one awake. The researchers ascertained that fruit flies doze off in response to being shaken, and thus were the control subjects induced to snooze in their individual, warmed tubes. Each subject occupied its own 29 °C (84F) tube.

For their sleepless cohort, fruit flies were genetically manipulated to express a heat-sensitive protein in specific neurons. These neurons are known to suppress sleep, and did so — the fruit flies' activity levels, or lack thereof, were tracked using infrared beams.

Starting at Day 10 of sleep deprivation, fruit flies began dying, with all of them dead by Day 20. Control flies lived up to 40 days.

The scientists sought out markers that would indicate cell damage in their sleepless subjects. They saw no difference in brain tissue and elsewhere between the well-rested and sleep-deprived fruit flies, with the exception of one fruit fly.

However, in the guts of sleep-deprived fruit flies was a massive accumulation of ROS, which peaked around Day 10. Says Vaccaro, "We found that sleep-deprived flies were dying at the same pace, every time, and when we looked at markers of cell damage and death, the one tissue that really stood out was the gut." She adds, "I remember when we did the first experiment, you could immediately tell under the microscope that there was a striking difference. That almost never happens in lab research."

The experiments were repeated with mice who were gently kept awake for five days. Again, ROS built up over time in their small and large intestines but nowhere else.

As noted above, the administering of antioxidants alleviated the effect of the ROS buildup. In addition, flies that were modified to overproduce gut antioxidant enzymes were found to be immune to the damaging effects of sleep deprivation.

The research leaves some important questions unanswered. Says Kaplan Dor, "We still don't know why sleep loss causes ROS accumulation in the gut, and why this is lethal." He hypothesizes, "Sleep deprivation could directly affect the gut, but the trigger may also originate in the brain. Similarly, death could be due to damage in the gut or because high levels of ROS have systemic effects, or some combination of these."

The HMS researchers are now investigating the chemical pathways by which sleep-deprivation triggers the ROS buildup, and the means by which the ROS wreak cell havoc.

"We need to understand the biology of how sleep deprivation damages the body so that we can find ways to prevent this harm," says Rogulja.

Referring to the value of this study to humans, she notes,"So many of us are chronically sleep deprived. Even if we know staying up late every night is bad, we still do it. We believe we've identified a central issue that, when eliminated, allows for survival without sleep, at least in fruit flies."

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We must rethink the "chemical imbalance" theory of mental health.

Bottles of antidepressant pills named (L-R) Wellbutrin, Paxil, Fluoxetine and Lexapro are shown March 23, 2004 photographed in Miami, Florida.

Photo Illustration by Joe Raedle/Getty Images
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