Can We Stop Cancer Cells From Reading Their Own DNA?

Dekker and her team are trying to stop tumor development by interfering with the molecular motors that copy DNA during cell division. This will cut off the genetic information flow that tumours need to grow, and could complement existing cancer therapies, while in the longer term bringing the promise of improved outcomes with greatly reduced side effects.

There are three primary ways of treating cancer at present, and these have fundamentally changed little in 30 years. In the case of solid tumours, surgery can be used to cut out the cancerous tissue, while radiation therapy can kill the malignant cells, and chemotherapy stops them dividing. Dekker's work is aiming towards a new generation of drugs that target cancer cells much more specifically than traditional chemotherapy, avoiding side effects such as temporary hair loss.

Dekker is focusing on an enzyme called Topoisomerase IB that plays a key role in some of the molecular motors involved in the processes of DNA and RNA copying during cell division. These are responsible for reading the genetic code and making sure it is encoded correctly in the daughter cell. In healthy cells it is important that this process works normally, but in cancer cells it is a natural target for disruptive therapy. "Specifically targeting these molecular motors in cancer cells would then prevent the cancer cells from growing into a larger tumor," said Dekker.

This molecular copying machinery, constructed mostly out of proteins, in effect walks along the DNA double helix reading the genetic code so that it can be copied accurately into new DNA during division. Other components of the machinery are responsible for slicing and assembling the DNA itself. All of these are potential targets for anti-cancer therapy, providing it is possible to single out the tumor cells. Most existing chemotherapy targets all dividing cells, and the aim to find more sensitive techniques.

However Dekker's work is not just confined to cancer, having the broader goal within the ESF EURYI project of unraveling the underlying physical principles behind these molecular motors that operate at the nanometer scale to process and manipulate the information stored within the DNA and RNA of our cells. Dekker is exploiting a variety of new highly sensitive manipulation and imaging techniques capable of resolving single molecules. These include force spectroscopy, new forms of optical microscopy with greatly improved resolving power and field depth, as well as nanotechnologies.

The research involves cross-disciplinary work among scientists in different fields with the long term goal of developing more precisely targeted molecular medicines for a variety of diseases involving disruption to normal cellular functions and not just cancer.

Dekker's work has already shown great promise, and she has been able to predict what effect certain antitumor drugs would have on the basis of her molecular insights, confirming her hypotheses in yeast cells. "Indeed the work with antitumor drugs is, as far as I know, the first experiment in which single-molecule experiments have resulted in a prediction for a cellular effect," said Dekker.