Fly Genes of the Past: The Future of Cancer Research?

Rachel Kim, an ordinary young girl who loved to swim, was looking forward to her upcoming second birthday.  In June 2003, she awoke one day with a fever that lasted for two whole weeks.  Rachel began to complain of leg pains and her family noticed that her stomach was distended.

One month later, when the Kims took Rachel to the pool, she uncharacteristically cried and refused to play.  Suspecting that something was wrong with their daughter, the Kims took Rachel to her pediatrician who reported a shocking diagnosis.  Rachel had neuroblastoma.

A rare form of cancer afflicting only 700 children in the USA each year, neuroblastoma affects the sympathetic nervous system, a network of nerves which carries messages from the brain to the rest of the body.  Most neuroblastomas first develop in the abdomen — probably the reason for Rachel’s swelling belly.  The cancer then spreads to the bones, bone marrow, liver, and other areas of the body — prompting Rachel’s leg complaints.

“Rachel had stage IV cancer.  She was going to die”

-Angela Kim, Rachel’s mother

Risky Treatments: New technologies utilize antibodies that recognize a single specific molecule to target cancer cells and kill them with radiation. However, these treatments may be dangerous and further research needs to be conducted before this strategy can become widely adopted.

Risky Treatments: New technologies utilize antibodies that recognize a single specific molecule to target cancer cells and kill them with radiation. However, these treatments may be dangerous and further research needs to be conducted before this strategy can become widely adopted.

We still don’t know how neuroblastoma is caused; however, we do know that a small number of cases are genetically linked.

Rachel’s parents decided to transfer her to one of the top cancer centers in the country. There, she was subject to a variety of intense therapies that caused her much pain. Fortunately, the treatment seemed to be working.  Three days before completing the protocol, though, a new tumor was discovered in Rachel’s brain.  Rachel’s family almost lost hope — generally, once the tumor reaches the brain it becomes untreatable.

Desperate for a miracle, Rachel’s parents agreed to have her enrolled in a clinical trial for a new experimental treatment that used antibodies to target neuroblastoma cells and subject them to radiation.  Rachel was the first person to ever receive this treatment. Generally, risky treatments are first tested on animal models of the respective disease to determine their efficacy, risks, and potential problems.  However, neuroblastoma exclusively affects humans; it is impossible to find a naturally-occurring case among animals in the wild.

“The treatment had never been tested on animals.  Rachel and her parents were brave.”

– Rachel’s Pediatric Oncologist

Luckily, Rachel didn’t experience much pain with this treatment and ultimately, her case was a success.  However, other candidates were not as fortunate and many could not receive treatment since it was not and could not be tested on animals.

The Needle in the Genomic Haystack

What are the next steps for bringing neuroblastoma treatment to a larger population?  To answer this question, scientists have turned to a century-old finding by Thomas Hunt Morgan.  One day in 1910, Morgan was sitting at his lab bench in the humid fly room at Columbia University when he noticed something amiss; one male fly had white eyes instead of the usual red-colored eyes.

While this observation may sound trivial, it was actually quite the contrary.  Morgan had discovered the first Drosophila melanogaster, or fruit fly, mutant and used his discovery to prove the chromosome theory.  This fundamental theory of genetics recognizes chromosomes as genetic carriers (Beebe, 2010).  Morgan’s seemingly simple determination earned him a Nobel Prize, but also had effects in a different area.  His findings profoundly changed the way we use animals for biomedical research and motivated scientists to consider these flies as potential animal models.

Thomas Hunt Morgan, circa 1891. Morgan confirmed the chromosome theory through tests on fruit flies.  See page for author [Public domain], via Wikimedia Commons.

Thomas Hunt Morgan, circa 1891. Morgan confirmed the chromosome theory through tests on fruit flies.
See page for author [Public domain], via Wikimedia Commons.

Indeed, Morgan’s research from the early twentieth century, along with a groundbreaking modern discovery, has provided insight into future neuroblastoma treatment (Miko, 2008).

With the high-risk forms of the disease having only a 30% survival rate, researchers continue to search for the genetic root of neuroblastoma in order to develop new treatments.  Recently, scientists at the University of Pennsylvania made a discovery that may be able to help bring these treatments to widespread use.  Their 2008 study identified a major cause of genetically-based neuroblastoma — a germline mutation in the anaplastic lymphomakinase (ALK) gene (Mossé et al.).

The discovery of the ALK mutation opens new strategies for disease treatment, but also hints at new ways of artificially creating animal models of neuroblastoma that otherwise would not exist (Mossé et al., 2008).  Compensating for the mutated ALK gene in patients can create a novel therapeutic.  Further, by mimicking the effects of the mutation, neuroblastoma can be effectively induced in animals, thereby creating a new model..

However, most organisms do not contain the ALK gene and are therefore unsuitable to model neuroblastoma.  Fortunately, Drosophilae have the gene.

In the same way Thomas Morgan observed Drosophila mutants with white eyes, researchers can now artificially create Drosophilae with mutated ALK genes.

Drosophila melanogaster, or the fruit fly, can potentially serve as a model for neuroblastoma since they have the ALK gene.

Drosophila melanogaster, or the fruit fly, can potentially serve as a model for neuroblastoma since they have the ALK gene.

Looking Forward

In the future, scientists may be able to test new neuroblastoma treatments in Drosophilae before administering high-risk treatment to children.  Drosophilae are easier to maintain than larger animal models and have genomes that are very similar to those of humans.  In addition, the connections between various cancers and diseases might allow small modifications of this system to be applicable to other cases.

While Rachel was lucky to have had success with an untested experimental treatment, other patients with neuroblastoma may one day receive medication that has been thoroughly tested.  By continually incorporating modern findings with established knowledge to improve the accuracy of animal models, we will one day reach our ultimate goal of helping other children achieve Rachel’s success.

In Brief:

  • Neuroblastoma is a rare form of cancer that doesn’t occur in the wild– only in humans
  • Scientists have recently found that neuroblastoma is caused by a mutation in the anaplastic lymphoma kinase (ALK) gene
  • Drosophila melanogaster, or fruit flies, also have the ALK gene and may be able to serve as animal models for this rare disease

Works Cited

This article was written by cYw8. As always, before leaving a response to this article please view our Rules of Conduct. Thanks! -cYw Editorial Staff

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