Different reactions to the same dose of chemotherapy
The most common drugs used for chemotherapy treatments of childhood cancers kill the cancer cells by damaging their DNA. But, in the process the DNA in healthy cells is also damaged. The drugs need to kill the tumour, but there must be a balance to make sure the damages in the normal cells are minimised. This is complicated since people react differently to the same dose of chemotherapy.
“All cells have mechanisms to repair damaged DNA, since DNA in the cells can break for various reasons. Some individuals have genetic variations, and the enzymes involved in the DNA-repair might not work properly. In these individuals a “normal” dose of drugs used for chemotherapy might cause extra damage to healthy cells,” says Fredrik Westerlund.
Blood sample will detect hypersensitivity
By using nature’s own systems for DNA-repair the researchers will use the new method to quantify DNA-damage. The long-term aim is that a blood sample from cancer patients will detect individuals that are hypersensitive to cytostatic drugs in an early stage of treatment, to be able to adjust the dosage before too much damage is done. In this way families with genetic defects could also be detected, and if needed, have individualised future cancer treatments.
Every DNA-break is counted one by one using a fluorescence microscope, but in the future the method should enable easier handling of samples in clinical practise. The physicians at Sahlgrenska University Hospital are already working with adaption of other methods for clinical use, which should be of great use for this project as well.
“Our method is a development of a project we started in 2016, funded by the Swedish Childhood Cancer Foundation. We believe that we have found a way to decrease suffering for patients in the future,” says Fredrik Westerlund.
Diagnosis of acute leukaemia
The other project, also a collaboration with a research group at Sahlgrenska University Hospital, is method development for diagnosis of acute leukaemia. Several types of leukaemia are caused by large fragments of DNA being shifted from one chromosome to another. This leads to the production of proteins that should not be present in normal cells, which then can transform into cancer cells.
The method, still in an early stage of development, will be used to find the location of the DNA break. This resembles the classic problem to look for a needle in a haystack, since the human genome consists of billions of bases and only one single DNA break is of interest. To find the exact position of the damage is crucial since the treatment differs for different breaks.
Important to treat leukaemia at an early stage
Fredrik Westerlund has been working on a method for mapping DNA for a long time, but with focus on bacterial DNA. In this project human DNA will be studied. Two strategies will be used. One where huge amounts of DNA are mapped to find “the needle”, and another for isolation of only the “needle” of interest.
“Leukaemia is one of the cancers where early treatment is of great importance. We believe that this method will we be relatively quick for diagnosis, enabling treatment and giving the patient the right dose in an early stage of the disease,” says Fredrik Westerlund.
Text: Susanne Nilsson Lindh
Photo: Johan Bodell
Facts: Fredrik Westerlund’s grants from Barncancerfonden (The Swedish Childhood Cancer Foundation)
Project grant Improved cancer treatment for children sensitive to DNA damage:
- A project in collaboration with Ola Hammarsten, Professor and Chief Physician at Sahlgrenska University Hospital, the University of Gothenburg.
- Grant amount: 2,4 million SEK.
Project grant medical technology Improved diagnosis of acute leukaemia in children:
- A project in collaboration with Linda Fogelstrand, MD and Associate Professor at Sahlgrenska University Hospital, the University of Gothenburg.
- Grant amount: 3 million SEK.