Ravi Bellamkonda, lead investigator for the GBM
project and chair of the Wallace H. Coulter
Department of Biomedical Engineering at Georgia
Tech and Emory University, is shown with
equipment used to study the cancer.
Credit: Georgia Tech Photo: Rob Felt
Abstract:
One factor that makes glioblastoma cancers so
difficult to treat is that malignant cells from the
tumors spread throughout the brain by following
nerve fibers and blood vessels to invade new
locations. Now, researchers have learned to hijack
this migratory mechanism, turning it against the
cancer by using a film of nanofibers thinner than
human hair to lure tumor cells away.
Researchers hijack cancer migration mechanism
to 'move' brain tumors
Atlanta, GA | Posted on February 17th, 2014
Instead of invading new areas, the migrating cells
latch onto the specially-designed nanofibers and
follow them to a location - potentially outside the
brain - where they can be captured and killed.
Using this technique, researchers can partially
move tumors from inoperable locations to more
accessible ones. Though it won't eliminate the
cancer, the new technique reduced the size of
brain tumors in animal models, suggesting that
this form of brain cancer might one day be
treated more like a chronic disease.
"We have designed a polymer thin film nanofiber
that mimics the structure of nerves and blood
vessels that brain tumor cells normally use to
invade other parts of the brain," explained Ravi
Bellamkonda, lead investigator and chair of the
Wallace H. Coulter Department of Biomedical
Engineering at Georgia Tech and Emory
University. "The cancer cells normally latch onto
these natural structures and ride them like a
monorail to other parts of the brain. By providing
an attractive alternative fiber, we can efficiently
move the tumors along a different path to a
destination that we choose."
Details of the technique were reported February
16 in the journal Nature Materials. The research
was supported by the National Cancer Institute
(NCI), part of the National Institutes of Health; by
Atlanta-based Ian's Friends Foundation, and by
the Georgia Research Alliance. In addition to the
Coulter Department of Biomedical Engineering, the
research team included Children's Healthcare of
Atlanta and Emory University.
Treating the Glioblastoma multiforme cancer, also
known as GBM, is difficult because the aggressive
and invasive cancer often develops in parts of the
brain where surgeons are reluctant to operate.
Even if the primary tumor can be removed,
however, it has often spread to other locations
before being diagnosed.
New drugs are being developed to attack GBM,
but the Atlanta-based researchers decided to take
a more engineering approach. Anjana Jain, who is
the first author of this GBM study, is now an
assistant professor in the Department of
Biomedical Engineering at Worcester Polytechnic
Institute in Massachusetts. As a Georgia Tech
graduate student, Jain worked on biomaterials for
spinal cord regeneration. Then, as a postdoctoral
fellow in the Bellamkonda lab, she saw the
opportunity to apply her graduate work to develop
potential new treatment modalities for GBM.
"The signaling pathways we were trying to
activate to repair the spinal cord were the same
pathways researchers would like to inactivate for
glioblastomas," said Jain. "Moving into cancer
applications was a natural progression, one that
held great interest because of the human toll of
the disease."
Tumor cells typically invade healthy tissue by
secreting enzymes that allow the invasion to take
place, she explained. That activity requires a
significant amount of energy from the cancer
cells.
"Our idea was to give the tumor cells a path of
least resistance, one that resembles the natural
structures in the brain, but is attractive because
it does not require the cancer cells to expend any
more energy," she explained.
Experimentally, the researchers created fibers
made from polycaprolactone (PCL) polymer
surrounded by a polyurethane carrier. The fibers,
whose surface simulates the contours of nerves
and blood vessels that the cancer cells normally
follow, were implanted into the brains of rats in
which a human GBM tumor was growing. The
fibers, just half the diameter of a human hair,
served as tumor guides, leading the migrating
cells to a "tumor collector" gel containing the
drug cyclopamine, which is toxic to cancer cells.
For comparison, the researchers also implanted
fibers containing no PCL or an untextured PCL
film in other rat brains, and left some rats
untreated. The tumor collector gel was located
physically outside the brain.
After 18 days, the researchers found that
compared to other rats, tumor sizes were
substantially reduced in animals that had received
the PCL nanofiber implants near the tumors.
Tumor cells had moved the entire length of all
fibers into the collector gel outside the brain.
While eradicating a cancer would always be the
ideal treatment, Bellamkonda said, the new
technique might be able to control the growth of
inoperable cancers, allowing patients to live
normal lives despite the disease.
"If we can provide cancer an escape valve of
these fibers, that may provide a way of
maintaining slow-growing tumors such that, while
they may be inoperable, people could live with the
cancers because they are not growing," he said.
"Perhaps with ideas like this, we may be able to
live with cancer just as we live with diabetes or
high blood pressure."
Before the technique can be used in humans,
however, it will have to undergo extensive testing
and be approved by the FDA - a process that can
take as much as ten years. Among the next steps
are to evaluate the technique with other forms of
brain cancer, and other types of cancer that can
be difficult to remove.
Treating brain cancer with nanofibers could be
preferable to existing drug and radiation
techniques, Bellamkonda said.
"One attraction about the approach is that it is
purely a device," he explained. "There are no
drugs entering the blood stream and circulating in
the brain to harm healthy cells. Treating these
cancers with minimally-invasive films could be a
lot less dangerous than deploying pharmaceutical
chemicals."
Seed funding for early research to verify the
potential for the technique was sponsored by
Ian's Friends Foundation, an Atlanta-based
organization that supports research into
childhood brain cancers.
"We couldn't be more thrilled with the progress
that Georgia Tech and Professor Bellamkonda's
lab have made in helping find a solution for
children with both inoperable brain tumors and for
those suffering with tumors in more invasive
areas," said Phil Yagoda, one of the
organization's founders. "With this research
team's dedication and vision, this exciting and
exceptional work is now closer to reality. By
enabling the movement of an inoperable tumor to
an operable spot, this work could give hope to all
the children and parents of those children fighting
their greatest fight, the battle for their lives."
###
In addition to those already mentioned, the
research team included Barunashish Brahma from
the Department of Neurosurgery at Children's
Healthcare of Atlanta; Tobey MacDonald from the
Department of Pediatrics at Emory University
School of Medicine, and Martha Betancur,
Gaurangkuma Patel, Chandra Valmikinathan,
Vivek Mukhatyar, Ajit Vakharia and S. Balakrishna
Pai from the Wallace H. Coulter Department of
Biomedical Engineering at Georgia Tech and
Emory University.
This research was supported by the National
Cancer Institute of the National Institutes of
Health (NIH) through EUREKA award number
R01-CA153229. Any conclusions or opinions are
those of the authors and do not necessarily
represent the official views of the NIH.
project and chair of the Wallace H. Coulter
Department of Biomedical Engineering at Georgia
Tech and Emory University, is shown with
equipment used to study the cancer.
Credit: Georgia Tech Photo: Rob Felt
Abstract:
One factor that makes glioblastoma cancers so
difficult to treat is that malignant cells from the
tumors spread throughout the brain by following
nerve fibers and blood vessels to invade new
locations. Now, researchers have learned to hijack
this migratory mechanism, turning it against the
cancer by using a film of nanofibers thinner than
human hair to lure tumor cells away.
Researchers hijack cancer migration mechanism
to 'move' brain tumors
Atlanta, GA | Posted on February 17th, 2014
Instead of invading new areas, the migrating cells
latch onto the specially-designed nanofibers and
follow them to a location - potentially outside the
brain - where they can be captured and killed.
Using this technique, researchers can partially
move tumors from inoperable locations to more
accessible ones. Though it won't eliminate the
cancer, the new technique reduced the size of
brain tumors in animal models, suggesting that
this form of brain cancer might one day be
treated more like a chronic disease.
"We have designed a polymer thin film nanofiber
that mimics the structure of nerves and blood
vessels that brain tumor cells normally use to
invade other parts of the brain," explained Ravi
Bellamkonda, lead investigator and chair of the
Wallace H. Coulter Department of Biomedical
Engineering at Georgia Tech and Emory
University. "The cancer cells normally latch onto
these natural structures and ride them like a
monorail to other parts of the brain. By providing
an attractive alternative fiber, we can efficiently
move the tumors along a different path to a
destination that we choose."
Details of the technique were reported February
16 in the journal Nature Materials. The research
was supported by the National Cancer Institute
(NCI), part of the National Institutes of Health; by
Atlanta-based Ian's Friends Foundation, and by
the Georgia Research Alliance. In addition to the
Coulter Department of Biomedical Engineering, the
research team included Children's Healthcare of
Atlanta and Emory University.
Treating the Glioblastoma multiforme cancer, also
known as GBM, is difficult because the aggressive
and invasive cancer often develops in parts of the
brain where surgeons are reluctant to operate.
Even if the primary tumor can be removed,
however, it has often spread to other locations
before being diagnosed.
New drugs are being developed to attack GBM,
but the Atlanta-based researchers decided to take
a more engineering approach. Anjana Jain, who is
the first author of this GBM study, is now an
assistant professor in the Department of
Biomedical Engineering at Worcester Polytechnic
Institute in Massachusetts. As a Georgia Tech
graduate student, Jain worked on biomaterials for
spinal cord regeneration. Then, as a postdoctoral
fellow in the Bellamkonda lab, she saw the
opportunity to apply her graduate work to develop
potential new treatment modalities for GBM.
"The signaling pathways we were trying to
activate to repair the spinal cord were the same
pathways researchers would like to inactivate for
glioblastomas," said Jain. "Moving into cancer
applications was a natural progression, one that
held great interest because of the human toll of
the disease."
Tumor cells typically invade healthy tissue by
secreting enzymes that allow the invasion to take
place, she explained. That activity requires a
significant amount of energy from the cancer
cells.
"Our idea was to give the tumor cells a path of
least resistance, one that resembles the natural
structures in the brain, but is attractive because
it does not require the cancer cells to expend any
more energy," she explained.
Experimentally, the researchers created fibers
made from polycaprolactone (PCL) polymer
surrounded by a polyurethane carrier. The fibers,
whose surface simulates the contours of nerves
and blood vessels that the cancer cells normally
follow, were implanted into the brains of rats in
which a human GBM tumor was growing. The
fibers, just half the diameter of a human hair,
served as tumor guides, leading the migrating
cells to a "tumor collector" gel containing the
drug cyclopamine, which is toxic to cancer cells.
For comparison, the researchers also implanted
fibers containing no PCL or an untextured PCL
film in other rat brains, and left some rats
untreated. The tumor collector gel was located
physically outside the brain.
After 18 days, the researchers found that
compared to other rats, tumor sizes were
substantially reduced in animals that had received
the PCL nanofiber implants near the tumors.
Tumor cells had moved the entire length of all
fibers into the collector gel outside the brain.
While eradicating a cancer would always be the
ideal treatment, Bellamkonda said, the new
technique might be able to control the growth of
inoperable cancers, allowing patients to live
normal lives despite the disease.
"If we can provide cancer an escape valve of
these fibers, that may provide a way of
maintaining slow-growing tumors such that, while
they may be inoperable, people could live with the
cancers because they are not growing," he said.
"Perhaps with ideas like this, we may be able to
live with cancer just as we live with diabetes or
high blood pressure."
Before the technique can be used in humans,
however, it will have to undergo extensive testing
and be approved by the FDA - a process that can
take as much as ten years. Among the next steps
are to evaluate the technique with other forms of
brain cancer, and other types of cancer that can
be difficult to remove.
Treating brain cancer with nanofibers could be
preferable to existing drug and radiation
techniques, Bellamkonda said.
"One attraction about the approach is that it is
purely a device," he explained. "There are no
drugs entering the blood stream and circulating in
the brain to harm healthy cells. Treating these
cancers with minimally-invasive films could be a
lot less dangerous than deploying pharmaceutical
chemicals."
Seed funding for early research to verify the
potential for the technique was sponsored by
Ian's Friends Foundation, an Atlanta-based
organization that supports research into
childhood brain cancers.
"We couldn't be more thrilled with the progress
that Georgia Tech and Professor Bellamkonda's
lab have made in helping find a solution for
children with both inoperable brain tumors and for
those suffering with tumors in more invasive
areas," said Phil Yagoda, one of the
organization's founders. "With this research
team's dedication and vision, this exciting and
exceptional work is now closer to reality. By
enabling the movement of an inoperable tumor to
an operable spot, this work could give hope to all
the children and parents of those children fighting
their greatest fight, the battle for their lives."
###
In addition to those already mentioned, the
research team included Barunashish Brahma from
the Department of Neurosurgery at Children's
Healthcare of Atlanta; Tobey MacDonald from the
Department of Pediatrics at Emory University
School of Medicine, and Martha Betancur,
Gaurangkuma Patel, Chandra Valmikinathan,
Vivek Mukhatyar, Ajit Vakharia and S. Balakrishna
Pai from the Wallace H. Coulter Department of
Biomedical Engineering at Georgia Tech and
Emory University.
This research was supported by the National
Cancer Institute of the National Institutes of
Health (NIH) through EUREKA award number
R01-CA153229. Any conclusions or opinions are
those of the authors and do not necessarily
represent the official views of the NIH.
