A gene screening technique developed by Juha Rantala lies behind the new finding.
Why do cancer cells sustain DNA damage? Why do cancer cells, unlike normal cells, fail to die as a result of DNA damage? Cancer researchers’ concern in finding the mechanism was ended by its discovery through a microchip method developed by Juha Rantala.
Thanos Halazonetis and Jiri Bartek first proposed in 2008 the activation of a specialized DNA repair mechanism in tumour cells experiencing oncogene induced replication stress. This mechanism repairs the damage caused by forced DNA replication in cancer cells, but also results in errors, such as mutations, and changes in DNA copy numbers. Researchers were then able to undertake further research to uncover new information on cancer initiation and progression.
VTT’s Medical Biotechnology unit in Turku had the necessary competence, cell screening equipment and RNAi libraries to perform this further research.
The study results reveal that the repair mechanism is activated in cancer cells already in the early stages of the disease, in connection with the activation of oncogenes.
Oncogene activation causes so-called ’DNA replication stress’ as cancer cells begin to replicate their genome faster than a healthy cell. Chromosomes break up and the normal DNA structure changes.
– We showed that the mechanism causing genomic changes in cancer cells is caused by the oncogene itself, and not by an external factor. We believe this to be a fundamental mechanism involved in majority, if not all types of cancers, Dr Juha Rantala explains.
– Growth at the initial stage of cancer is not always malignant, but we can already detect DNA breaks caused by replication stress and indicating the development of cancer. The tumour develops, there are further genomic changes and the cancer cell becomes increasingly malignant as the cell’s normal regulation mechanisms are disrupted.
This new information is ready for immediate use in cancer research.
– Microchip-based screening was a brand new method in 2004 when I finished my studies and started working for VTT. My competence in various technologies meant that development of microchip technology using robotics became a natural part of my job, says Rantala.
The microchip method enables use of complex assay techniques for screening that would be impossible with traditional methods. The first version of the research method based on RNA interference was developed in the USA in 2003 by Professor Olli Kallioniemi and his team.
The traditional screening method enables measurement with one microtitre plate of the functioning of a few hundred genes. The cell microchip screening method developed by Rantala is up to 100 times more efficient, with widespread uses for a number of measurement and screening needs. The method also creates savings in research costs since the amount of expensive reagents, or culture mediums, needed for growing cancer cells, and RNA molecules used for gene silencing, is much smaller compared to traditional screening.
– This tool enables us to produce findings that will accelerate the development of future cancer medicines. The reliability and versatility of this method has been proven in several research projects, says Rantala.
The research results are now openly available to researchers.
The method based on cell microchips is up to 100 times more efficient than the traditional method.
Juha Rantala works as Research Professor in the Knight Cancer Institute at the Oregon Health & Science University (OHSU), one of the USA’s fastest-developing cancer research centres. The university is particularly renowned for its research on leukaemia and other blood and heart diseases.
– Last year, we achieved very interesting new findings in the field of breast cancer, and are working on a few high impact publications. Our future aim is to be able to define rapidly the best suited treatment for each patient that will be as effective as possible. The key to this is screening examination of drug collections using the patient’s own cells, says Rantala.
A finding on a DNA repair mechanism known as Break Induced Replication Repair (BIR), published in Science magazine in December 2013, has not been described before in either human or mammal animal cells. Cancer cells use the mechanism to repair DNA damage resulting from uncontrolled DNA replication.
The genes that participate in the repair mechanism were discovered by Juha Rantala and Thanos Halazonetis. Among others participating in the study was Thomas Helleday from the Karolinska Institutet.
The research was part of the EU’s GENICA project.