Starving melanoma cells may slow tumor growth

Date: Feb-19-2014New research suggests melanoma skin cancer may be controllable by starving its

cells. Building on previous success with prostate cancer cells, scientists in Australia showed

they could stop cell growth by blocking the pumps that melanoma cells use to acquire an

essential cell nutrient.

It is still very early days, as the method has only been tested in lab-grown cells. But the

researchers, from Sydney's Centenary Institute and the University of Sydney, hope their

findings will lead to new drugs that

control a range of cancers, including melanoma.

They report their new work on melanoma cells in The International Journal of

Cancer.

While melanoma is the least common skin cancer, it is responsible for the most deaths. In

Australia, it is the third most common cancer. Australia also has the highest rate of melanoma in

the world.

The American Cancer Society estimates that in 2014, about 76,100 Americans will discover they

have melanoma and about 9,710 will die of the disease.

Blocking glutamine pump in melanoma cells stopped them growing

Normal cells rely on glucose to fuel their energy needs so they can grow and divide. But

melanoma and other cancer cells rely on the amino acid glutamine instead, which they suck in via

pumps scattered over their cell surface.

In this new study, lead author Dr. Jeff Holst and colleagues discovered that not only do melanoma cells have more glutamine

pumps on their surface, but also when they blocked these pumps it stopped them growing.

They successfully demonstrated this using lab-cultured cells and a compound called BenSer,

which is known to block the kind of amino acid pump they were targeting. They note in their

study paper:

"Cell proliferation and cell cycle progression were significantly reduced in the presence of

BenSer in melanoma cells in 2D and 3D cell culture."

Dr. Holst says:

"We've shown that if we starve melanoma of these essential nutrients, we can stop the cancer

from growing. This involves blocking the protein pumps that move glutamine into tumor cells,

which successfully slowed the growth of the tumors in cell cultures."

Although melanoma is more curable if detected early, it is very difficult to treat once it

has spread, as it rapidly develops resistance to known drugs. This new finding is important

because, as Dr. Holst explains, "a drug that specifically targets and inhibits the glutamine

pump will give us a new and different approach from current treatments."

Blocking nutrient pumps could be new way of treating range of cancers

Mathew Vadas, executive director of the Centenary Institute, adds: "This work is leading a new wave with potential to develop cancer therapeutic agents."

The researchers estimate it will be 5 to 10 years before a drug that blocks the glutamine

pump is available to melanoma patients.

In 2011, Dr. Holst and colleagues reported how they discovered they could starve prostate cancer cells by

cutting off their supply of the amino acid leucine.

"We first demonstrated this nutrient pumping mechanism in prostate cancers, and it now looks

like it occurs in a broad range of cancers, particularly solid cancers such as melanoma," he

explains, adding that "this opens the possibility of designing therapies that can be used to block nutrient pumps

across multiple cancers."

Written by Catharine Paddock PhD




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