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Nano 'Basketballs' to Battle Drug-Resistant Cancer

Eric Bland, Discovery News

Cancer cells evolve resistance to drugs in several ways, including blocking the channels drugs use to enter cancer cells or devising more efficient means to pumping them out if the drugs do get in.

The gene SIRT1, for instance, helps cells regulate their metabolism and nutrient intake. Gottesman and his colleagues discovered that expressing the SIRT1 gene slows the cancer cell's metabolism. In essence, SIRT1 allows cancer cells to slow the cell's metabolism, giving them time to collect the anticancer drugs and pump them out of the cell before they do too much damage.

The research was published recently in the journal Molecular Cancer Research.

Identifying the genes responsible for drug-resistant cancer is the first step. The next step is turning them off.

Gavin Robertson, a researcher at Pennsylvania State University, is turning off cancer resistance genes using hollow basketball-shaped nanoparticles called nanoliposomes. The nano basketballs ferry small pieces of RNA (siRNA) that interfere with gene expression into cancer cells.

Once inside, the siRNA silences two mutated genes, B-Raf and Atk3, which together could play a role in up to 70 percent of malignant melanomas, a cancer that can be especially drug resistant. The research appears in the journal Cancer Research.

Gene mutations aren't always identical however, and a drug that targets one person's gene mutation might not work for another. The advantage of an approach like Robertson's is that he could tailor the siRNA molecules to each person's individually mutated, drug-resistant cancer genes. In military terms, that's like moving from World War II-style carpet bombing to modern GPS and laser-guided weapons.

These molecular weapons are still five years away from human use and still await Food and Drug Administration approval, says Robertson, but it could make cancer treatment less painful.

"This would be truly personalized medicine," said Robertson. "We could tailor our drugs to each person's specific DNA to create more effective drugs that have fewer side effects."

Related Links:

The Cancer Collage

Penn State College of Medicine

How Stuff Works: Cancer