Effects of drugs on cancer cells

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Cancer cells are transformed body cells that human body cannot control, discovering weakness of cancer cells can aid its treatment In certain types of breast and ovarian cancer, for example, such a weakness is given by mutations in genes that play a role in DNA repair. Treating breast and ovarian cancer cells with a group of newly approved drugs- PARP inhibitors makes it difficult for these cells to replicate their DNA. Normal and healthy cells can solve the problems using their DNA.

The Department of Molecular Mechanisms of Disease of the University of Zurich uses cancer cell cultures to investigate the exact effects of this new group of drugs. The method of fluorescence-based high-throughput microscopy allows researchers to observe precisely when and how a drug works in thousands of cells at the same time.

There measurements have revealed how PARP inhibitors lock their target protein in an inactive state on the cells’ DNA and how this complicates DNA replication, which in turn leads to DNA damage. If this damage is not repaired quickly, the cells can no longer replicate and eventually die.

The new approach enables researchers to analyze the initial reaction of cancer cells to PARP inhibitors with great precision. High number of individual cells can be analyzed concurrently with high resolution using the automated microscopes. Cancer cells vary and  react differently to drugs depending on their mutations and the cell cycle phase they are in.

In some patients, the cancer returns after a certain point, the cancer cells become resistant and no longer respond to the drugs. Cells can be tested in multiple conditions with short turnover times, and specific genes can be eliminated one by one in a targeted manner. This reveal which cell functions are needed for a certain drug to take effect.

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