In the early 1900s, American biologist Thomas Hunt Morgan and his students at Columbia University began breeding Drosophila melanogaster, commonly known as fruit flies, in order to better understand the development of animal embryos. Little did they know then that more than a century of scientific research using fruit flies would lead to six Nobel Prizes and make this small animal a cornerstone of our understanding of genetics, development, evolution, and medicine. Fruit flies have about 14,000 genes compared with 24,000 in humans. Most genes involved in the development of the fly are also essential for normal mammalian development. Adult fruit flies have body parts that mimic mammalian hearts, kidneys, digestive tracts, and lungs. Furthermore, fruit flies share some 70 percent of the genes responsible for human disease. Fruit fly genes are not the same as human genes, but they are sufficiently similar in structure and function that they can be an effective tool for research in human diseases. Importantly, because the life of a fruit fly is short, only about 50 days from birth to death and two weeks from birth to adulthood, experiments using flies can be done quickly. And because flies are inexpensive to house, this can be done very cost effectively. These attributes have made the fly a premier model organism for discovering fundamental and evolutionarily conserved biological mechanisms. Fruit flies have also proven instrumental in researching human diseases. For example, most human cancer genes were discovered through analogues in flies. Recently, the fruit fly has been harnessed as a tool in drug discovery, providing a model test system to screen drugs for their activity in treating human diseases such as cancer and neurogenerative diseases. A leader in this field is the California biopharmaceutical company Tosk, Inc. Tosk has developed two new drug screening technologies using fruit flies. The most advanced product in Tosk’s pipeline was the first drug discovered in the fly to enter human clinical studies. Known as TK-90, this drug selectively blocks gastrointestinal side effects caused by cancer therapies. It has demonstrated efficacy in head and neck cancer patients receiving high doses of chemotherapy. TK-90 is a new chemical entity with a novel mechanism of action. It was discovered using a model Tosk calls the Side Effect Fly™. Two other drugs have been discovered by Tosk using this method, Tk-39 for cardiotoxicity side effect prevention and TK-88 for nephrotoxicity side effect prevention. In addition to improving the quality of life for patients, side effect prevention holds the potential to improve the efficacy of cancer therapies by allowing increased dosing. And because side effects can be costly to treat, side effect prevention also has the potential to reduce the overall cost of cancer care. Tosk has developed a second fly-based drug screening model to test compounds for their ability to block the activity of cancer genes.

1. The Role of Fruit Flies in Oncology
Brian Frenzel

2. Introduction
In the early 1900s, American biologist Thomas Hunt Morgan and his students at
Columbia University began breeding Drosophila melanogaster, commonly known as
fruit flies, in order to better understand the development of animal embryos. Little
did they know then that more than a century of scientific research using fruit flies
would lead to six Nobel Prizes and make this small animal a cornerstone of our
understanding of genetics, development, evolution, and medicine.

3. Fruit flies have about 14,000 genes compared with 24,000 in humans. Most genes
involved in the development of the fly are also essential for normal mammalian
development. Adult fruit flies have body parts that mimic mammalian hearts,
kidneys, digestive tracts, and lungs. Furthermore, fruit flies share some 70 percent
of the genes responsible for human disease. Fruit fly genes are not the same as
human genes, but they are sufficiently similar in structure and function that they
can be an effective tool for research in human diseases. Importantly, because the
life of a fruit fly is short, only about 50 days from birth to death and two weeks from
birth to adulthood, experiments using flies can be done quickly. And because flies
are inexpensive to house, this can be done very cost effectively. These attributes
have made the fly a premier model organism for discovering fundamental and
evolutionarily conserved biological mechanisms.

4. Fruit flies have also proven instrumental in researching human diseases. For
example, most human cancer genes were discovered through analogues in flies.
Recently, the fruit fly has been harnessed as a tool in drug discovery, providing a
model test system to screen drugs for their activity in treating human diseases
such as cancer and neurogenerative diseases.

5. A leader in this field is the California biopharmaceutical company Tosk, Inc. Tosk
has developed two new drug screening technologies using fruit flies. The most
advanced product in Tosk’s pipeline was the first drug discovered in the fly to enter
human clinical studies. Known as TK-90, this drug selectively blocks
gastrointestinal side effects caused by cancer therapies. It has demonstrated
efficacy in head and neck cancer patients receiving high doses of chemotherapy.

6. TK-90 is a new chemical entity with a novel mechanism of action. It was discovered
using a model Tosk calls the Side Effect Fly™. Two other drugs have been
discovered by Tosk using this method, Tk-39 for cardiotoxicity side effect
prevention and TK-88 for nephrotoxicity side effect prevention. In addition to
improving the quality of life for patients, side effect prevention holds the potential to
improve the efficacy of cancer therapies by allowing increased dosing. And because
side effects can be costly to treat, side effect prevention also has the potential to
reduce the overall cost of cancer care.

7. Tosk has developed a second fly-based drug screening model to test compounds
for their ability to block the activity of cancer genes. Known as the Genetically
Modified Fly™, this model involves integrating a human cancer gene into the
genome of a fruit fly so that flies emerge from larva with deformed wings. Tosk
then screens drugs that inhibit the cancer gene’s activity, resulting in a more normal
wing. This new drug discovery method has been deployed to discover drugs that
block the activity of certain mutant cancer genes known as oncogenic KRAS genes.
These genes drive as many as 30% of all cancers.

8. Results like these bode well for the continued use of Drosophila melanogaster in
medical research and drug discovery. Perhaps fly research will yield another six
Nobel Prizes in the coming decades, along with important drugs to address unmet
medical needs.