Scientists don’t really know what kills many cancer patients, but fruit fly research could provide answers. By following flies with tumors up to the point of death, researchers have discovered chemicals produced by tumors that shorten life span apart from the damage done locally to critical organs. This suggests a novel strategy for extending a healthy life span in those with a cancer burden, block the tumor-generated chemicals and the damage they do.
A research conducted at the University of California, Berkley shows that a fruit fly dying from cancer may seem worlds away from that of a human with a life-threatening tumor. Those researchers are finding commonalities between the two that could lead to ways to prolong the lives of cancer patients.
Fruit fly research is already pointing to a new anti-cancer strategy distinct from the conventional goal of destroying the tumor or cancerous cells. Instead, the research suggests, launching an attack against the destructive chemicals the cancer is throwing off could increase survival rates and improve patients’ health.
Jung Kim, a postdoctoral fellow in Bilder’s lab, recently discovered that tumors in fruit flies release a chemical that compromises the barrier between the bloodstream and the brain, letting the two environments mix a recipe for disaster in numerous diseases, including infection, trauma and even obesity.
In collaboration with the labs of University of Berkeley, Professors David Raulet and Kaoru Saijo, Kim and Bilder subsequently demonstrated that tumors in mice that release the same chemical, a cytokine called interleukin-6 (IL-6), also make the blood-brain barrier leaky.
More importantly, they were able to extend the lifespan of both fruit flies and mice with malignant tumors by blocking the effect of the cytokine on the barrier.
The IL-6 cytokine is known to cause inflammation. What’s new here is that this tumor induced inflammation is actually causing the blood brain barrier to open. If it is interfered with that opening process but leave the tumor alone, then the host can live significantly longer and healthier with the same tumor burden.
IL-6 plays other important roles in the body, so to benefit cancer patients, scientists would have to find a drug that blocks its action at the blood-brain barrier without altering its effects elsewhere. But such a drug could potentially extend the life span and health span of human cancer patients.
Six years ago, Bilder’s team found that tumors in fruit flies also release a substance that blocks the effects of insulin, providing a potential explanation for the tissue wasting called cachexia that kills one-fifth of all cancer patients. That work is now being explored by numerous labs around the world.
One advantage of helping the host fend off a tumor’s effects on tissues far from the tumor site is that it could potentially reduce or even eliminate the need for toxic drugs typically used to subdue tumors. Such drugs also harm the patient, killing healthy cells as well as cancerous cells.
Up to date, scientists still are uncertain what causes death in many cancer patients. Cancer of the liver, for example, clearly destroys the function of an organ essential for life.
However, other organs, like the skin or the ovaries, are less critical, yet people die from cancer in these sites, too, sometimes very quickly. And though cancers often metastasize to other organs, multiple organ failure is one of the main causes of cancer death listed by doctors.
According to researchers, many human cancers are metastatic, but that doesn’t change the basic question: “Why does the cancer kill?”. “If your tumor metastasized to the lung, are you dying because of lung failure or are you dying from something else?”
For that reason, those researchers at Berkley University works with non-metastatic tumors implanted in fruit flies and mice and looks for systemic effects, not merely the effects on the tumor-containing organ itself.
Studying cancer in fruit flies offers several advantages over cancer models in other animals, such as mice and rats. For one thing, researchers can follow flies right up to the moment of death, in order to determine what actually causes mortality. Ethical concerns prevent researchers from allowing vertebrates to suffer, so research animals are euthanized before they die naturally, preventing a full understanding of the ultimate cause of death. For these animals, tumor size is used as a proxy to assess an animal’s chance of survival.
And while most cancer studies in rodents involve just a few dozen animals, fruit fly experiments can involve many hundreds of individuals, which improve the statistical significance of the results. Fruit flies also reproduce quickly and have short natural life spans, allowing quicker studies.
The research shows that fruit flies and humans are only distantly related, but in the past, these flies “Drosophila melanogaster “ have played a key role in understanding tumor growth factors and ontogenesis. Fruit flies now could also be key in understanding cancer’s systemic effects.