A new approach established at the University of Zurich, Switzerland, sheds light on the effects of drugs on cancer cells. The method makes it possible to quickly test various drugs and treatment combinations at the cellular level.
Cancer cells are the cells that the human body has lost control of, and since they are transformed body cells, it makes it more difficult to combat them effectively. Usually, what harms cancer cells, also harms the healthy cells in the body. Now, a new study investigates the effects of drugs on cancer cells and how to treat them.
In certain types of cancer, such a weakness is given by mutations in genes that play a role in DNA repair. Treating cancer cells of this kind with a group of newly approved drugs – so-called PARP inhibitors – makes it difficult for these cells to replicate their DNA, and they ultimately perish. Normal cells, however, can solve such problems using their intact DNA repair machinery.
The effect of drugs observed in thousands of cells
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. Researcher Jone Michelena said: “Our method of fluorescence-based high-throughput microscopy allows us to observe precisely when and how a drug works in thousands of cells at the same time.”
As reported by the university, Michelena’s measurements have discovered how PARP inhibitors lock their target protein on the cell’s DNA and how this complicates DNA replication, which in turn leads to DNA damage. If this damage is not repaired rapidly, the cells can no longer replicate and eventually die.
The new approach enables researchers to analyse the initial reaction of cancer cells to PARP inhibitors with great precision and therefore measure the effects of drugs on cancer cells.
What’s different about the very sensitive procedure is the high number of individual cells that can be analysed simultaneously with high resolution using the automated microscopes at the Center for Microscopy and Image Analysis of UZH.
Cancer cells vary and thus react differently to drugs depending on their mutations and the cell cycle phase they are in.
Precise testing of cancer cells
The success of PARP inhibitors and other cancer medication is made complex by the fact that in some patients the cancer returns, and that after a certain point the cancer cells become resistant and no longer respond to the drugs.
The new method employed by the researchers is useful for this issue as cells can be tested in multiple conditions, and specific genes can be eliminated one by one in a targeted manner. Doing so can reveal which cell functions are needed for specific drugs to take effect.
Matthias Altmeyer, head of the research group at the Department of Molecular Mechanisms of Disease, concludes: “We hope that our approach will make the search for strategies to combat cancer even more efficient.”