{"id":46155,"date":"2023-09-20T12:00:00","date_gmt":"2023-09-20T12:00:00","guid":{"rendered":"https:\/\/www.cancer.gov\/news-events\/cancer-currents-blog\/2023\/engineered-bacteria-detect-cancer"},"modified":"2024-11-03T15:12:23","modified_gmt":"2024-11-03T15:12:23","slug":"could-bacteria-help-find-cancer","status":"publish","type":"post","link":"https:\/\/ogkologos.com\/en\/could-bacteria-help-find-cancer\/","title":{"rendered":"Could Bacteria Help Find Cancer?"},"content":{"rendered":"

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Researchers have programmed bacteria to become “biosensors,” seeking out and capturing tumor DNA with mutations in the KRAS<\/em> gene.<\/p>\n

Credit: National Cancer Institute<\/p>\n<\/p><\/div>\n<\/figcaption><\/figure>\n<\/p><\/div>\n

A team of US and Australian scientists has engineered bacteria that can detect DNA that has been released from tumors.<\/p>\n

In a new study, the team showed that, in mice, their engineered \u201cbacterial biosensors\u201d picked up mutated DNA shed into the gut by colorectal tumors<\/a>.<\/p>\n

The bacteria are programmed to go on a sort of molecular manhunt, seeking and capturing DNA with mutations in the KRAS<\/em> gene. When the mutated DNA is captured, a genetic switch is tripped, triggering the bacteria to put out a signal indicating that cancer was detected. <\/p>\n

The results were published August 11 in Science<\/em>.<\/p>\n

In addition to detecting cancer noninvasively, these bacterial biosensors could possibly be designed to diagnose the precise type of cancer they\u2019re finding, said Miguel Ossandon, Ph.D., of NCI\u2019s Division of Cancer Treatment and Diagnosis (DCTD)<\/a>, who was not involved in the research.<\/p>\n

There\u2019s also the potential to use the engineered bacteria to deliver treatments to tumors in the gut when and where they\u2019re detected, said one of the study\u2019s senior investigators, Daniel Worthley, M.D., Ph.D., of the Colonoscopy Clinic in Brisbane, Australia. In other words, \u201cto unite diagnosis and therapy,\u201d Dr. Worthley said.<\/p>\n

At least one previous study<\/a> has reported the engineering of bacteria to detect cancer. But, according to DCTD’s Avraham Rasooly, Ph.D., who also was not involved in the work, this study describes the most advanced engineering of bacteria specifically for cancer detection and, potentially, diagnosis. <\/p>\n

However, Dr. Rasooly added, much more work is needed before the approach could be used in people.<\/p>\n

And the new technology won\u2019t replace colonoscopy\u2014at least, not anytime soon, Dr. Worthley said. Colonoscopy is still the best way to find and remove precancerous growths in the gut, he noted. <\/p>\n

Bacteria can take up DNA from their environment<\/h2>\n

To create the biosensors, the scientists exploited a natural ability of many bacteria. The bacteria can grab free-floating DNA from their environment and stitch it into their own genomes in place of a similar piece of DNA, explained co-lead investigator Robert Cooper, Ph.D., of the University of California San Diego. Under normal circumstances, this ability lets bacteria gain new traits that help them grow and survive.<\/p>\n

The team used a type of bacteria called Acinetobacter baylyi<\/em> that\u2019s especially good at pulling in DNA from its surroundings. A. baylyi<\/em> bacteria can live in a mouse\u2019s gut but \u201care generally not found in people,\u201d Dr. Cooper said.<\/p>\n

Using genetic engineering techniques, the scientists programmed the bacteria to find and take up snippets of KRAS<\/em>. Harmful mutations in KRAS<\/em> fuel many cases of colorectal cancer and other cancers, including lung and pancreatic.<\/p>\n

The team further rigged the bacteria so that if they take up one particularly harmful form of mutated KRAS<\/em> called G12D, they respond by switching on a gene that makes them resistant to the antibiotic kanamycin. Resistance to kanamycin can easily be detected in the lab by seeing if the bacteria grow in the drug\u2019s presence.<\/p>\n

Testing the engineered bacteria<\/h2>\n

In a series of lab dish experiments, the team showed that the engineered bacteria could detect DNA containing KRAS<\/em> G12D from lab-grown colorectal cancer cells and organoids (mini-organ-like structures). Bacteria that took up KRAS<\/em> G12D\u2014but not normal, unmutated KRAS<\/em>\u2014were able to grow in petri dishes laden with kanamycin.<\/p>\n

Finally, the team delivered the engineered bacteria directly into the gut of mice with or without colorectal tumors. Only A. baylyi<\/em> bacteria recovered from the gut of animals with tumors grew in the presence of kanamycin. And the genomes of those bacteria were shown to contain the altered KRAS<\/em> gene.<\/p>\n

For this initial set of experiments, Drs. Worthley and Cooper explained, they used an optimized system to ensure the best chances of success. That included using tumor DNA engineered in the lab as the \u201cdonor DNA\u201d to be picked up by the engineered bacteria.<\/p>\n

Once the team had shown that their basic engineering concept worked, they further engineered A. baylyi<\/em> to detect \u201cnatural, non-engineered\u201d tumor DNA. <\/p>\n

So far, Dr. Cooper said, this retooled biosensor \u201cwill work in a lab dish but is not accurate enough to work well in mice,\u201d meaning it could give false-negative as well as false-positive results. However, he said, \u201cwe think that\u2019s a surmountable obstacle.\u201d<\/p>\n

One thing is clear, the research team and experts not involved in the study agreed: More work is needed to develop and fine-tune the new technology for possible use in cancer care. <\/p>\n

That will include adapting the system for use with types of bacteria that are better suited for human use, such as those that are able to live in the human gut, and developing a way to deliver the bacteria by mouth. It also means further engineering and testing the system to ensure it\u2019s safe.<\/p>\n

And to apply the approach beyond cancers of the gut, more research will be needed to engineer bacteria \u201cso they are able to get into less-accessible tumors, like those in the pancreas,\u201d Dr. Ossandon said.<\/p>\n

A “modular” and adaptable approach<\/h2>\n

\u201cThis is a novel approach \u2026 that has a lot of potential to build on and improve,\u201d said Claudia Gravekamp, Ph.D., of Albert Einstein College of Medicine, who works on bacteria-based cancer therapies and vaccines and was not involved in the new study. <\/p>\n

Because the bacteria are engineered with components that can easily be switched out, the approach \u201cis adaptable to detecting other types of known cancer-causing mutations and could be applied to a number of different settings,\u201d said Phil Daschner, M.S., a program director in NCI\u2019s Division of Cancer Biology<\/a>, which funded the work.<\/p>\n

One advantage of this \u201cmodular\u201d genetic engineering technique, Dr. Cooper explained, is that \u201cwe can easily tell the bacteria to look for other bits of DNA,\u201d and to respond in different ways once cancer is detected. <\/p>\n

For example, he continued, the bacteria might be engineered to produce a compound that is easily detected in a urine or blood sample instead of becoming resistant to an antibiotic.<\/p>\n

And while the proof-of-principle study was limited to detecting a single KRAS<\/em> mutation often seen in colorectal cancer, the bacteria could also be engineered to detect mutations more commonly found in other types of cancer, Daschner said.<\/p>\n

Indeed, Dr. Cooper said, the team hopes to engineer the bacteria to detect more than one genetic mutation at a time.<\/p>\n

Another potential advantage of the new approach compared with other tests that screen for cancer, Daschner said, is that \u201cthe bacteria can detect the mutated DNA where it is, [and] when the mutation happens.\u201d <\/p>\n

DNA is often destroyed by enzymes in the gut, \u201cso unless there\u2019s a lot of tumor DNA, other tests, such as [existing] stool-based tests, might not detect it in a sample,\u201d he continued. <\/p>\n

Envisioning a wide range of possible clinical uses<\/h2>\n

For Dr. Worthley, the real long-term promise of the engineered bacteria is as a form of targeted therapy, not just as a way to look for cancer. Because the bacteria \u201ccan respond directly at the time and place of disease detection,\u201d he explained, they could be used to deliver treatments on the spot once cancer\u2014or even a precancerous lesion\u2014is detected.<\/p>\n

Dr. Worthley holds stock in a company that is developing engineered bacteria for cancer therapy, which was co-founded by another senior author on the study, Jeff Hasty, Ph.D., of UC San Diego.<\/p>\n

On the other hand, Drs. Rasooly and Ossandon believe the most exciting potential of the technology, which was not discussed in the study, is as a noninvasive alternative to tissue biopsy for diagnosing and monitoring cancer.  <\/p>\n

Instead of a tissue biopsy, which may involve a large needle or surgery, they said, engineered bacteria could someday be used to \u201csample\u201d tumor DNA from the gut\u2014and perhaps also tumors in other parts of the body\u2014and deliver the DNA for genetic analysis. This could potentially revolutionize cancer biopsy and diagnosis, Dr. Rasooly said.<\/p>\n

However, Dr. Ossandon noted, this possible application is \u201cway in the future.\u201d<\/p>\n

In the nearer term, Dr. Gravekamp proposed, the engineered bacteria could be used outside the body as a sensitive way to detect specific cancer-related mutations in patient blood samples. <\/p>\n

\u201cIf [the researchers] were able to get that working, it would be beautiful and may be applicable to so many cancers,\u201d she said.<\/p>\n

Source<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

September 20, 2023, by Elia Ben-Ari Researchers have programmed bacteria to become “biosensors,” seeking out and capturing tumor DNA with mutations in the KRAS gene. Credit: National Cancer Institute A team of US and Australian scientists has engineered bacteria that can detect DNA that has been released from tumors. In a new study, the team showed that, […]<\/p>\n","protected":false},"author":2,"featured_media":46156,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_monsterinsights_skip_tracking":false,"footnotes":""},"categories":[5137],"tags":[],"class_list":["post-46155","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-world-news"],"_links":{"self":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/46155","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/comments?post=46155"}],"version-history":[{"count":1,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/46155\/revisions"}],"predecessor-version":[{"id":46262,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/46155\/revisions\/46262"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/media\/46156"}],"wp:attachment":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/media?parent=46155"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/categories?post=46155"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/tags?post=46155"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}