FRUIT FLYS: CONTRIBUTE TO CANCER RESEARCH

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At first glance, a fruit fly’s experience with cancer might seem nothing like what a human goes through. But researchers at UC Berkeley are finding striking similarities that could open up new ways to help people with cancer live longer.

Instead of the usual approach—trying to destroy tumors—this research suggests a different tactic: fighting the harmful chemicals that tumors release into the body. The hope is that by targeting these chemicals, it might be possible to improve cancer patients’ health and survival without directly attacking the tumor itself.

“It’s a complementary approach to cancer therapy,” explains David Bilder, a molecular and cell biology professor at UC Berkeley. “Rather than focusing on killing the tumor, we’re looking at how to help the body handle the damage caused by the tumor.”

One of the key discoveries, made by postdoctoral researcher Jung Kim in Bilder’s lab, is that tumors in fruit flies release a chemical that weakens the barrier between the blood and the brain. This causes the two environments to mix—a dangerous situation that’s involved in several diseases. When Kim and colleagues worked with other Berkeley labs, they found that tumors in mice produce the same chemical, interleukin-6 (IL-6), which also disrupts the blood-brain barrier.

The breakthrough came when blocking the effects of IL-6 in both fruit flies and mice led to more prolonged survival, even though the actual tumors remained.

“IL-6 is known for causing inflammation, but what’s new here is that tumor-induced inflammation is opening up the blood-brain barrier,” Bilder says. “If we can stop that process—without touching the tumor—the host can live significantly longer and healthier, even with the same tumor burden.”

Because IL-6 has other vital roles in the body, any potential treatment would need to block its effect at the blood-brain barrier specifically, without interfering elsewhere. Still, this approach could eventually help extend and improve the lives of human cancer patients.

This research builds on Bilder’s earlier work from six years ago, when his team found that tumors in fruit flies also produce a substance that blocks insulin, offering a possible explanation for the muscle wasting, called cachexia, that kills about 20% of cancer patients. That finding is now being explored in labs around the world.

One advantage of this host-focused approach is that it might allow doctors to use fewer toxic drugs, which can damage healthy cells as well as cancer cells.

Targeting tumor cells also has another downside: it encourages drug resistance, because tumors are genetically diverse and can evolve to survive treatment. In contrast, targeting the body’s response could be more effective, since normal cells are genetically stable and unlikely to develop resistance. Bilder says this is their ultimate goal: to understand how tumors affect the body as a whole and find ways to intervene on the host side.

Their findings on IL-6 and the blood-brain barrier were published last week in Developmental Cell, and Bilder also wrote a recent review in Nature Reviews Cancer about the impact of fruit fly research on our understanding of how tumors interact with their hosts. The earlier cachexia study appeared in Developmental Cell in 2015.

What causes death in cancer patients remains a mystery. In some cases, like liver cancer, the disease destroys a vital organ. But in other cases, people die from cancers in less essential organs, like the skin or ovaries, sometimes quite rapidly. Doctors often cite multiple organ failure, mainly when cancer spreads, but Bilder suggests there’s more to the story.

“Even with metastatic cancers, the core question remains: What exactly kills the patient?” he says. “Is it organ failure, or is something else going on?”

To get at this question, Bilder’s group studies non-metastatic tumors in fruit flies and mice, focusing on how cancer affects the entire body, not just the organ with the tumor.

Cachexia, or severe weight and muscle loss, is one such systemic effect. Bilder’s research points to chemicals released by tumors that interfere with insulin, while other scientists have identified additional waste-producing substances.

The new study suggests that blood-brain barrier breakdown could be another long-range effect of tumors. Blocking IL-6 activity at this barrier increased the lifespan of fruit flies with cancer by 45%. In mice, 21 days after treatment with an IL-6 receptor blocker, 75% of cancer-bearing mice survived, compared to just 25% of untreated mice.

But Bilder says the story isn’t as simple as just a leaky blood-brain barrier causing death: “Flies can survive several weeks with a compromised barrier, but if they also have a tumor, they die quickly. It suggests the tumor might be releasing something that becomes deadly once it passes through the broken barrier—or perhaps something harmful moves from brain to blood.”

Bilder’s lab has also linked tumor-produced chemicals in flies to fluid retention and blood clotting—two problems common in many cancer patients. Other teams have found links to appetite loss and immune system issues.

Studying cancer in fruit flies has special advantages. Researchers can observe the flies’ entire lifespan—including the moment of death—providing more precise information about how cancer kills. That’s not possible in mice or rats, which must be euthanized before they suffer, so tumor size becomes the primary measure of survival. Fruit flies also reproduce quickly, have short natural lifespans, and experiments can include hundreds of individuals, which makes results more statistically robust.

Of course, fruit flies and humans are distant relatives. Still, Drosophila melanogaster has already helped scientists unlock secrets about tumor growth and cancer genes. Now, this tiny insect could help us understand how cancer affects the body as a whole.

“Flies can develop tumors that look like human cancers, and now we’re seeing that the body’s response—cachexia, blood problems, immune changes, cytokine production—mirrors what happens in people,” Bilder says. “There’s a lot to learn here. We hope our work draws more attention to this field, from both fly researchers and cancer biologists.”

The new paper’s co-authors include UC Berkeley postdoc Hsiu-Chun Chuang, graduate student Natalie Wolf, and former doctoral student Christopher Nicolai. Grants from the National Institutes of Health supported the research.