Endogenous viruses in cancer treatment

The top image shows human ovarian tissue. The blue colouring shows the individual cell nuclei. The brown colouring in the bottom image shows the activation of an endogenous retrovirus gene. (Image: PD Dr. Strissel/PD Dr. Reiner Strick)
The top image shows human ovarian tissue. The blue colouring shows the individual cell nuclei. The brown colouring in the bottom image shows the activation of an endogenous retrovirus gene. (Image: PD Dr. Strissel/PD Dr. Reiner Strick)

FAU researchers identify inactive genes that could help treat cancer

August 28, 2015

The human genome is made up of many genes. Some of these are foreign genes – viruses that became integrated into genes over the course of evolution. Most of these are inactive. However, if they are activated they can stimulate the human immune system – which may help to treat cancer. These are the results of a new study carried out by researchers at FAU in collaboration with colleagues in the USA. The researchers recently published their findings in the renowned journal Cell.*

The genetic information for humans is carried in genes. The time and place where a gene is active is regulated exactly in each cell. This process is important for normal cell development but also plays a key role in the growth of tumours. It has been known for some time that there are substances – known as DNA methylation inhibitors (DMI) – that stimulate a large number of the immune system’s genes in cancer cells, helping to combat the tumour. In clinical trials carried out with lung cancer patients in the USA it was possible to improve the treatment of patients significantly by administering DMI before immunotherapy.

However, it remained unclear how the DMI improved the cancer patients’ treatment. An international team of researchers from the USA and FAU have now provided an explanation of the molecular and cellular causes. DMI activate human endogenous retroviruses. These endogenous retroviruses became integrated into the human genome over the course of evolution, but then mostly became inactive.

Using endogenous viruses to treat cancer

In their project the researchers treated ovarian cancer cells with DMI. They discovered that the DMI activated genes that led to the formation of interferons – types of protein with anti-tumour effects – which in turn led to the death of the cancer cells. Furthermore, the researchers observed that the DMI caused double-stranded RNA to form. This is a nucleic acid that is essential for protein synthesis on the basis of genetic information and is usually an indication of a viral infection. Indeed, the team of researchers led by PD Dr. Reiner Strick from FAU’s Chair of Obstetrics and Gynaecology were able to show that the RNA came from the family of endogenous retroviruses.

The activated endogenous retroviruses therefore stimulate the immune response. The researchers were also able to demonstrate this function in other lung, skin and breast cancers. This allowed them to categorise the tumours into different groups according to how strongly the endogenous retroviruses were activated. ‘Initial pre-clinical studies involving skin cancer have shown that simultaneous DMI treatment and immunotherapy has a higher and more permanent success rate,’ Strick explains. ‘Now that we know how DMI work we may be able to use it to improve cancer treatment in the future.’

Further information:

PD Dr. Reiner Strick
Phone: +49 9131 8536671
reiner.strick@uk-erlangen.de