New blood test developed for early diagnosis of ovarian cancer

Research on a bacterial toxin first discovered in Adelaide has led to the development a new blood test for the early diagnosis of ovarian cancer - a disease which kills over 1000 Australian women and 150,000 globally each year.

The new blood test has the potential to dramatically improve early detection of the disease, although it will require further testing before it is available for clinicians.

A research team from the University of Adelaide and Griffith University have been studying the interactions between the toxin and an abnormal glycan (sugar) expressed on the surface of human cancer cells and released into the blood.

The team has now engineered a harmless portion of the toxin to enhance its specificity for the cancer glycan and used this to detect it in blood samples from women with ovarian cancer.

A paper published this month in Biochemical and Biophysical Research Communications has shown that the new test detected significant levels of the cancer glycan in blood samples from over 90% of women with stage 1 ovarian cancer and in 100% of samples from later stages of the disease, but not in any of the samples from healthy controls.

"Ovarian cancer is notoriously difficult to detect in its early stages, when there are more options for treatment and survival rates are better. Our new test is therefore a potential game changer," says Professor James Paton, Director of the University of Adelaide's Research Centre for Infectious Diseases.

Professor Michael Jennings, Deputy Director of the Institute for Glycomics at Griffith University, said: "Detection of this tumor marker may also play a role in a simple liquid biopsy to monitor disease stage and treatment."

The team is currently seeking scientific and commercial partners to further test the technology with larger numbers of patient samples and to adapt it for mass screening.

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Off/on switch for DNA repair protein

Damage to DNA is a daily occurrence but one that human cells have evolved to manage. Mayo researchers have determined how one DNA repair protein gets to the site of DNA damage. The authors say they hope this discovery research will help identify new therapies for ovarian cancer.

While the human genome is constantly damaged, cells have proteins that detect and repair the damage. One of those proteins is called 53BP1. It is involved in the repair of DNA when both strands break. In the publication, Georges Mer, a Mayo Clinic structural biologist, and his team report on how 53BP1 relocates to chromosomes to do its job.

Dr. Mer explains that, in the absence of DNA damage, 53BP1 is inactive and blocked by a protein called "TIRR." Using a visualization technique called X-ray crystallography, the researches showed that TIRR obstructs an area on 53BP1 that 53BP1 uses to bind chromosomes. But what shifts TIRR away from 53BP1, so the repair protein can work?

They theorized that the type of nucleic acid called RNA was responsible for this shift. To test their theory, they engineered a protein that would bind to the 53BP1 repair protein and the RNA molecules released when DNA is damaged. They reported that when DNA damage occurs, RNA molecules produced at that time can bind to TIRR, displacing it from 53BP1 and allowing 53BP1 to swing into action.

"Our study provides a proof-of-principle mechanism for how RNA molecules can trigger the localization of 53BP1 to DNA damage sites. The TIRR/RNA pair can be seen as an off/on switch that blocks or triggers 53BP1 relocation to DNA damage sites. " says Dr. Georges Mer. 

However they reported that displacing TIRR increases sensitivity of cells in cell culture to olaparib, a drug used to treat patients with ovarian cancer.

"Unfortunately, over time cancer cells develop resistance to drugs in this category, called 'PARP inhibitors.Our work provides a new target, TIRR, for developing therapeutics that would help specifically kill ovarian cancer cells," Dr. Mer says.

Our conference Cell Tissue Science 2019, mainly focuses on the complications the consequences of Cancer Cell Biology and Technical Advancements in cancer treatment. The speakers from different part of the world will be present their immense research talk on this specific topics. We welcome you to the our conference “ 12th World Congress on Cell & Tissue Science” .You can also present your latest research at our conference.For more info: Celltissue Science 2019