Discovery explains cancer chemotherapy resistance, offers solution

Researchers have uncovered a novel pathway that explains how cancer cells become resistant to chemotherapies, which in turn offers a potential solution for preventing chemo-resistance.

Experimental DNA fibers with fluorescence were used to reveal the speed of DNA replication forks.

The research describes for the first time how a type of enzyme — previously known for its roles in DNA repair — prevents DNA damage in cancer cells, making them tolerant to chemotherapy drugs.

“It provides us tools to manipulate and then break chemo-resistance in cancer cells,” said Marcus Smolka, interim director of the Weill Institute for Cell and Molecular Biology and professor of molecular biology and genetics in the College of Agriculture and Life Sciences. Diego Dibitetto, a former postdoctoral researcher in Smolka’s lab who is currently at the University of Bern in Switzerland, is the paper’s first author.

Many anti-cancer drugs work by creating blocks on the DNA of cancer cells as they replicate. During replication, DNA strands entwined in a double helix separate into two individual strands so each strand can be copied, eventually leading to two new double helixes. The junction where this separation and copying occurs is called a replication fork, which unzips down the double helix.

If these replication forks were cars on a road, chemotherapy drugs can be imagined as obstacles that interfere with the flow of the cars, thus stopping replication and breaking DNA. But cancer cells have a way of slowing down these forks, which allows them to avoid such collisions and protect their DNA, leading to drug tolerance.

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