Why don’t some cancers give up when we fight them with radiation and chemotherapy?
As this ScienCentral News video reports, one scientist thinks he might find some answers by figuring out how some tumor cells seal off cancer drugs so they don’t work.
Shedding Light on Cancer Right now, doctors can treat many cancer cases with medicine’s arsenal of radiation and chemotherapy. But some stubborn tumors refuse to respond to cancer drugs. Researchers can’t say why, mostly because they don’t know much about how tumor cells resist treatment. At New York’s Rockefeller University, a center of biological research, Nobel Laureate Gunter Blobel admits, “It’s shocking how little we know about how a cell works.”
Until recently, researchers didn’t have the tools to watch what happens inside living tumor cells. In another Rockefeller laboratory, biologist Sanford Simon believes that being able to see many components of a cell working together at once, might lead to treatments that no tumor can resist. He compares the limitations of traditional ways of studying a cell’s interactions to learning a board game from one player’s moves. “Let’s say I watched one game where I followed only my son’s moves. The next day I followed only my daughter’s moves. I wouldn’t understand how each player is affecting the other.”
To literally light up a cell’s insides, Simon has relied on fluorescence. He has taken advantage of natural fluorescence found in jellyfish, as well as in some chemotherapy drugs. He also has worked with a new nanotechnology tool, quantum dots– miniscule particles that glow under ultraviolet light. Most recently, Simon and his team have used fluorescence to watch the movements of certain protein molecules which, he says, look like inch worms as they transport drugs inside a tumor cell. To stop tumors from growing and spreading, cancer drugs must reach the cells’ nuclei, where they can destroy the tumor’s genetic material, or DNA. Tumor cells that resist drugs produce many more of these particular proteins, which researchers had thought worked like garbage trucks, carrying toxins such as cancer drugs out of cells.
Cancer cells resistant to drugs. image: Sanford Simon, Rockefeller University
Simon and his team took advantage of one chemotherapy drug’s natural fluorescence to track its travels via proteins inside breast-cancer tumor cells. They were surprised to find that tumor cells that resisted the drug contained as much of it as tumor cells that succumbed. The difference was that the proteins didn’t carry the drug to the cells’ nuclei. But the proteins hadn’t trucked the toxins outside the cells, either. Instead, they had simply stored them inside the cells, shutting them away from the nuclei in small compartments called lysosomes. Diverted by proteins to these storage units, the drugs are useless against a tumor after just a few hours.
Cancer cells resistant to drugs. image: Sanford Simon, Rockefeller University
Simon and his team took advantage of one chemotherapy drug’s natural fluorescence to track its travels via proteins inside breast-cancer tumor cells. They were surprised to find that tumor cells that resisted the drug contained as much of it as tumor cells that succumbed. The difference was that the proteins didn’t carry the drug to the cells’ nuclei. But the proteins hadn’t trucked the toxins outside the cells, either. Instead, they had simply stored them inside the cells, shutting them away from the nuclei in small compartments called lysosomes. Diverted by proteins to these storage units, the drugs are useless against a tumor after just a few hours.
Simon believes that what his team has seen so far “is a nice demonstration of the power of imaging to address questions that otherwise are inaccessible.” Next, since lysosomes act as cells’ garbage disposal units, Simon now wants to watch what happens to cancer drugs diverted there. “At some point, you have to take the garbage out. Does the cell run these toxins through a sort of garbage disposal so that they’re now dysfunctional?” What he’s able to see next, he says, could help design new treatments that may outwit drug-diverting proteins.
Simon’s research has been published most recently in Molecular Biology of the Cell. His work is funded by the American Cancer Society, National Institutes of Health (NIH), and the National Science Foundation (NSF).
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