Scientists Set To Use Ancient Enzymes To Rapidly Detect the Presence of Cancer Cells

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In a science report that may come as a form of relief to cancer patients undergoing treatment and people who are genetically prone to have cancer; a University of Texas research into ancient enzymes and biopsies is about to change how cancer cells can be detected quickly and profiled in the body.

Professor Alan Lambowitz of the Institute for Cellular and Molecular Biology and the Department of Molecular Biosciences, in the University of Texas, and his team of scientists are studying an ancient enzyme in bacteria which can be used to detect genetic materials shed by cancer cells, or bits of other diseased cells that are released into the bloodstream of a patient.

The research by the scientists is geared towards developing a set of medical tests termed ‘liquid biopsies’. These forms of biopsies are said to have the potential to rapidly detect infectious diseases in the body, presence of cancer and other medical conditions, from just a small sample of blood.

The project by the researchers at the Texas University is part of a new tool being developed which could provide doctors with more details about a patient’s disease.

Unlike surgical biopsies which are normally associated with long waits; the new tool called liquid biopsies would aid prompt and early detection thereby improving the chances the individual has of finding the best treatment, as well as sparing the person the pain and inconvenience synonymous with surgical biopsies.

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What are biopsies?

Various medical journals and professionals define biopsy in different ways, but common definitions include;

A biopsy is commonly performed as a medical test, by an interventional cardiologist, a surgeon, or an interventional radiologist, and it involves the extraction of sample cells or tissues for close examination to determine the presence or extent of a disease.

A biopsy is also define as a sample of tissue taken from the body in order to examine it more closely. A doctor should recommend a biopsy test for a patient when an initial test suggests that an area of tissue in the body isn't normal.

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How do liquid Biopsy Work?

There are liquid biopsies which currently exist today. Some of them can detect DNA in the blood. Some others can detect RNA. But the current liquid biopsies often miss many key RNA bio-markers and even misinterpret others.

But the ancient enzyme being described in a paper published recently in the Molecular Cell journal, has the ability to detect the full range of RNA’s with a high level of accuracy. This improved quality of the ancient enzyme would be helpful in understanding diseases, including the general profile of cancer diseases and also provide specific details about the disease’s activity within a particular patient system.

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Without a doubt, this improved method could provide a key tool enabling doctors to pursue the field of precision medicine, unique aspect of diseases and treatments which are based on the genetics and life histories of the affected individuals.

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The Research and Study

During the course of the new study, the molecular structure of this RNA-detecting enzyme was uncovered in action, by Jennifer Stamos a postdoctoral researcher. The discovery offered clues as to how the enzyme would work and how it can be used for further medical test applications.

DNAs and RNAs present in all living cells contain genetic details which are useful in understanding the state of a disease such as cancer, in the body.

The DNA which is found mainly in the nucleus of the cell is like a restaurant’s menu which contains all the information regarding the meals available for a customer to choose from. While, the RNA found mainly in the cytoplasm of the cell – although still synthesized in the nucleus – is like a customer’s order citing the quantity and types of meals requested.

According to Professor Alan Lambowitz;

“DNA biomarkers are static. They provide information about mutations that cause a disease, but they don’t provide information about the effect of these mutations on cellular processes, which can differ in different individuals,” said Lambowitz.

The limitation of the DNA marker is one of the reasons why a cancer-causing mutation can have varying effects on the individual, and also lead to different response to treatment.

Professor Lambowitz further said that;

By contrast, “Monitoring cellular RNAs provides a snapshot of exactly what is happening in diseased tissue, such as a tumor, at a particular time.”
“The method can be used to monitor day-to-day progression of the disease and response to treatment and to predict how different individuals with the same cancer will respond to different treatments.”

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The Ancient Bacterial Enzyme, GsI-IIC RT

Professor Alan Lambowitz alongside his team believe that this ancient enzyme called Gsl-IIC RT and some TGIRT group of enzymes, possess properties which make it easier to detect and profile RNA biomarkers observed from cancer cells and other disorders.

_{The molecular structure of this enzyme was revealed by postdoctoral researcher, Jennifer Stamos, for the first time}

An ancient bacterial enzyme (grey colour) is seen crawling along a tangled strand of RNA (orange colour), thus creating a complimentary strand of DNA (blue colour).

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Benefits of the GsI-IIC RT – ancient enzyme

Prof Lambowitz foresees a liquid biopsy method that when combined with other tools would provide a whole lot of information to health professionals.

Lambowitz studies the TGIRTs group of enzymes which he believes can help massively with cancer detection. TGIRTs helps to uncover RNA strands and then creates a complimentary strand of DNA to match it - this encodes the same information, and can be sequenced rapidly to reveal diagnostic information.

Prof Lambowitz also believes that because the TGIRTs can accurately make DNA copies of almost any type of RNA using very small starting materials, they would be better when it comes to catching biomarkers for diseases, unlike the currently available RNA-based liquid biopsies.

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Tests and Trials

Currently, Professor Lambowitz with his team are working together with clinicians to carry out tests on the liquid biopsies based on the TGIRT (ancient) enzyme.

One particular test and trial study going on at the University of Texas MD Anderson Cancer Center in Houston is focused on inflammatory breast cancer.

A second trial phase at the City of Hope National Medical Center near Los Angeles is focused on multiple myeloma. Multiple myeloma is a type form of cancer which affects the bone marrow.

Once the tests are confirmed successful, the new liquid biopsies would be applied together with other liquid biopsy techniques which are currently in use, such as the one which detects biomarkers of chromosomal abnormalities in a developing fetus of pregnant mothers, through their blood study.

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Approval and Patents

Co-author to the research study is Alfred Lentzsch. He is a molecular biosciences graduate. The study of the TGIRTs enzyme was supported by the Welch Foundation and the National Institutes of Health.

Professor Lambowitz and the Texas University are minority equity holders in InGex, a University of Texas spin-off company licensed with the patents and patent applications subject of the TGIRTs enzymes, as well as the method of their use.

Lambowitz, some of his present and former lab members, along with the University of Texas receive royalty payments generated from the sale and distribution of TGIRT enzymes, the kits and the intellectual property license.

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In conclusion

The TGIRTs are ancient enzymes which date back to the period when genetic information were stored mainly in RNA. But then, life was gradually transitioning to DNA.

The new study further showed that TGIRT enzymes are very similar to enzymes which come from RNA viruses and which copy the RNA. The study highlights the evolutionary role the TGIRTs ancient enzyme would play in the evolution of present day organisms that depend on DNA for genetic materials.

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Source/Reference: 1, 2, 3, 4, 5, 6, 7

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