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South Korean Study Finds Fecal Microbiota Transplants May Help Patients with Gastrointestinal Cancers That are Resistant to Immunotherapies

Study findings could lead to improved treatments for broad range of cancers and the need for microbiome testing by clinical laboratories to guide clinicians

Is it possible that there is a connection between an individual’s gut microbiota and the ability to fight off gastrointestinal (GI) cancer? Findings from a preliminary research study performed by researchers in South Korea suggest that a link between the two may exist and that fecal microbiota transplants (FMTs) may enhance the efficacy of immunotherapies for GI cancer patients. 

The proof-of-concept clinical trial, conducted at the Gwangju Institute of Science and Technology (GIST), Gwangju 61005, Republic of Korea, analyzed how an FMT could help 13 patients with metastatic solid tumors that were resistant to the anti-PD-1 antibody drug known as nivolumab (Opdivo). Anti-PD-1 drugs are immunotherapies that help treat cancer by improving an individual’s immune response against cancer cells. 

Four of the trial participants had gastric cancer, five had esophageal cancer, and the remaining four had hepatocellular carcinoma. The patients were given a colonoscopy to implant the FMTs. The recipients also received antibiotics to reduce the response of their existing microbiotas.

The FMT donors also had gastric cancer, esophageal cancer, or hepatocellular carcinoma. Prior to donating their fecal matter, the donors experienced complete or partial response to the anti-PD-1 drugs nivolumab or pembrolizumab (Keytruda) for at least six months after receiving initial treatments. 

The researchers published their study, titled, “Fecal Microbiota Transplantation Improves Anti-PD-1 Inhibitor Efficacy in Unresectable or Metastatic Solid Cancers Refractory to Anti-PD-1 Inhibitor,” in the journal Cell Host and Microbe.

“This research highlights the complex interplay between beneficial and detrimental bacteria within the gut microbiota in determining treatment outcomes,” co-senior study author Hansoo Park, MD, PhD, Assistant Professor, Biomedical Science and Engineering, Gwangju Institute of Science and Technology, told The ASCO Post. “While the connection between gut microbiota and immune response to cancer therapy has been a growing area of interest, our study provides concrete evidence and new avenues for improving treatment outcomes in a broader range of cancers,” he added. Further studies may confirm the need for microbiome testing by clinical laboratories to guide clinicians treating patients with colon cancers. (Photo copyright: Gwangju Institute of Science and Technology.)

Surprising Results

Fecal material for an FMT procedure combines donated fecal matter with a sterile saline solution which is then filtered to produce a liquid solution. That solution is then administered to the recipient via colonoscopy, upper GI endoscopy, enema, or an oral capsule. The solution may also be frozen for later use.

Upon analyzing the recipients, the scientists found that six of the patients (46.2%) who had experienced resistance to immunotherapies for their cancers, benefitted from the FMTs.

“One of the most surprising results was from a [patient with] hepatocellular carcinoma who initially showed no response to the first [FMT] and continued to experience cancer progression. However, after switching the donor for the second [transplant], the patient exhibited remarkable tumor shrinkage,” co-senior study author Sook Ryun Park, MD, PhD, Assistant Professor, Asan Medical Center at the University of Ulsan College of Medicine in Seoul, told The ASCO Post, a journal of the American Society of Clinical Oncology.

“Both donors were long-lasting, good responders to anti-PD-1 inhibitors, but because we did not yet know the causative bacteria responsible for the [FMT] response, we could not predict whether the treatment would be effective,” she added.

The researchers also determined that the presence of a bacterial strain known as Prevotella merdae helped to improve the effectiveness of the FMTs, while two strains of bacteria—Lactobacillus salivarius and Bacteroides plebeius (aka, Phocaeicola plebeius)—had a detrimental impact on the transplants. 

Challenges to Widespread Adoption of FMTs

The researchers acknowledge there are challenges in widespread acceptance and use of FMTs in treating cancers but remain optimistic about the possibilities.

“Developing efficient and cost-effective methods for production and distribution is necessary for widespread adoption,” Sook Ryun Park told The ASCO Post. “Addressing these challenges through comprehensive research and careful planning will be essential for integrating FMT into the standard of care for cancer treatment.”

The research for this study was supported by grants from the Asan Institute for Life Sciences, Asan Medical Center, National Cancer Centre in Korea, the GIST Research Institute, the Bio and Medical Technology Development Program from Ministry of Science, and the Ministry of Science and ICT of the South Korean Government.

More research and clinical trials are needed before this use of FMTs can be utilized in clinical settings. However, the study does demonstrate that the potential benefits of FMTs may improve outcomes in patients with certain cancers. As this happens, microbiologists may gain a new role in analyzing the microbiomes of patients with gastrointestinal cancers.

“By examining the complex interactions within the microbiome, we hope to identify optimal microbial communities that can be used to enhance cancer treatment outcomes,” Hansoo Park told The ASCO Post. “This comprehensive approach will help us understand how the microbial ecosystem as a whole contributes to therapeutic success.”

—JP Schlingman

Related Information:

Fecal Microbiota Transplant May Help Patients with Gastrointestinal Cancers Overcome Immunotherapy Resistance

Fecal Microbiota Transplantation Improves Anti-PD-1 Inhibitor Efficacy in Unresectable or Metastatic Solid Cancers Refractory to Anti-PD-1 Inhibitor

Fecal Microbiota Transplants Can Boost the Effectiveness of Immunotherapy in Gastrointestinal Cancers

Lancet Study Finds Urgent Need for Improvement in Clinical Laboratory Prostate Cancer Screening Worldwide

Ongoing increases in the global number of prostate cancer cases expected to motivate test developers to deliver better screening tests to pathologists and clinical lab scientists

No less an authority than the peer-reviewed healthcare journal The Lancet is drawing attention to predictions of increasing prostate cancer cases across the globe, triggering calls for the development of cheaper, faster, and more accurate assays that pathologists and medical laboratories can use to screen for—and diagnose—prostate cancer.

Swift population growth and rising life expectancy will cause the prostate cancer death rate to nearly double in the next 20 years, according to a new study that has led scientists to call for immediate, critical improvements in clinical laboratory testing for cancer screening, Financial Times (FT) reported.

The International Agency for Research on Cancer (IARC) partnered with The Lancet Commission for the study. They found the strongest need is with underserved populations.

“Low- and middle-income countries need to prepare to prevent a sharp rise in fatalities while richer nations should pay more attention to young men at higher risk of the disease,” FT noted. The study, titled, “The Lancet Commission on Prostate Cancer: Planning for the Surge in Cases,” predicts cases will jump from 1.4 million in 2020 to 2.9 million by 2040.

“Prostate cancer is the most common cancer in men in 112 countries, and accounts for 15% of cancers. In this Commission, we report projections of prostate cancer cases in 2040 on the basis of data for demographic changes worldwide and rising life expectancy. … This surge in cases cannot be prevented by lifestyle changes or public health interventions alone, and governments need to prepare strategies to deal with it,” the study authors wrote.

“The findings in this Commission provide a pathway forward for healthcare providers and funders, public health bodies, research funders, governments, and the broader patient and clinical community,” the authors noted. In their Lancet paper, the researchers define clear areas for improvement.

Given the shortage worldwide of pathologists—especially highly-trained pathologists—the gap between the demand/need for expanded prostate cancer testing as screens (along with prostate biopsies) and the available supply of pathologists will encourage companies to develop screening and diagnostic tests that are accurate and automated, thus increasing the productivity of the available pathologists.

“As more and more men around the world live to middle and old age, there will be an inevitable rise in the number of prostate cancer cases. We know this surge in cases is coming, so we need to start planning and take action now,” said Nick James, PhD (above), Professor of Prostate and Bladder Cancer Research at The Institute of Cancer Research, in a press release. Pathologists and medical laboratories worldwide will want to monitor progress of The Lancet Commission’s recommendations. (Photo copyright: Institute of Cancer Research.)

Focus on Outreach, AI, Research/Development

“The only thing you can do to mitigate the damage … is to set up programs that diagnose it earlier to allow earlier treatment,” Nick James, PhD, The Lancet Commission study’s lead author, told the Financial Times. James is Professor of Prostate and Bladder Cancer Research at The Institute of Cancer Research (IRC) and The Royal Marsden NHS Foundation Trust, London.

“Evidence-based interventions, such as improved early detection and education programs, will help to save lives and prevent ill health from prostate cancer in the years to come. This is especially true for low- and middle-income countries (LMICs) which will bear the overwhelming brunt of future cases,” he said in a press release.

Communication is key. “Improved outreach programs are needed to better inform people of the key signs to look out for and what to do next,” James N’Dow, MD, Professor and Chair in Surgery and Director of the Academic Urology Unit at the University of Aberdeen in the UK, told the Financial Times. “Implementing these in tandem with investments in cost-effective early diagnostic systems will be key to preventing deaths,” he added.

Capitalizing on artificial intelligence (AI) analysis to help translate results was another area The Lancet Commission researchers focused on, Financial Times noted.

AI could “subdivide disease into potentially valuable additional subgroups to help with treatment selection. In environments with few or no pathologists, these changes could be transformational,” the study authors wrote.

High Income Countries (HICs) would benefit from AI by empowering patients. “Linking cloud-based records to artificial intelligence systems could allow access to context-sensitive, up-to-date advice for both patients and health professionals, and could be used to drive evidence-based change in all settings,” the study authors added. Such a trend could lead to specialist prostate cancer pathologists being referred cases from around the world as digital pathology systems become faster and less expensive.

Effective treatment strategies and bolstering areas of need is also key, the study notes. “Many LMICs have urgent need for expansion of radiotherapy and surgery services,” the study authors wrote. The researchers stress the need to immediately implement expansion programs to keep up with anticipated near-future demand.

Cancer drug therapy should follow suit.

“Research and the development of risk-stratified regulatory models need to be facilitated,” the study authors noted, citing a focus on drug repurposing and dose de-escalation. “Novel clinical trial designs, such as multi-arm platforms, should be supported and expanded,” they added.

Unique Needs of LMICs, HICs

The Lancet Commission researchers’ recommendations shift depending on the financial health of a specific area. HICs are experiencing a 30-year decline in the number of deaths resulting from prostate cancer, presumably from additional testing measures and public health campaigns that may be lacking in LMICs, Financial Times reported. And as population growth soars, low-to-middle income populations “will need to be prepared for the strain the expected surge in cases will put on health resources.”

For HICs, the study dissected the limitations of prostate-specific antigen (PSA) testing. The researchers pointed out that PSA’s inaccuracies in screening symptomless patients can pinpoint “cancers that may never cause symptoms and need no treatment,” Financial Times reported.

Missing high-risk cases was also a cause for concern. “Diagnostic pathways should be modified to facilitate early detection of prostate cancer while avoiding overdiagnosis and overtreatment of trivial disease,” the study notes.

Screenings for high-risk younger men, and continuing public campaigns about prostate cancer, should be a focus for HICs, the study authors noted. “These would include people who have a family history of the disease, are of African ancestry, or carry a genetic mutation known as BRCA2,” Financial Times reported.

While the undertaking may sound intimidating—there is already such a heavy impact worldwide from prostate cancer—the researchers are optimistic of their recommendations.

“Options to improve care are already available at moderate cost. We found that late diagnosis is widespread worldwide, but especially in LMICs, where it is the norm. Early diagnosis improves prognosis and outcomes, and reduces societal and individual costs, and we recommend changes to the diagnostic pathway that can be immediately implemented,” the study authors wrote.

What Comes Next

“More research is needed among various ethnic groups to expand understanding of prostate cancer beyond the findings from studies that were largely based on data from white men,” The Lancet Commission told the Financial Times.

Astute pathologists and medical laboratories will want to monitor efforts to develop assays that are inexpensive, more accurate, and produce faster answers. Demand for these tests will be substantial—both in developed and developing nations.

—Kristin Althea O’Connor

Related Information:

Prostate Cancer Rise Sparks Call for Overhaul of Testing

The Lancet Commission on Prostate Cancer: Planning for the Surge in Cases

Lancet Commission Predicts Sharp Increase in Global Prostate Cancer Cases

The Lancet: Prostate Cancer Cases Expected to Double Worldwide Between 2020 and 2040, New Analysis Suggests

Prostate Cancer Cases Might Rise to 3 Million Globally by 2040

UK Researchers Use Artificial Intelligence to Identify DNA Methylation Signatures Associated with Cancer

Study findings could lead to new clinical laboratory diagnostics that give pathologists a more detailed understanding about certain types of cancer

New studies proving artificial intelligence (AI) can be used effectively in clinical laboratory diagnostics and personalized healthcare continue to emerge. Scientists in the UK recently trained an AI model using machine learning and deep learning to enable earlier, more accurate detection of 13 different types of cancer.

Researchers from the University of Cambridge and Imperial College London used their AI model to identify specific DNA methylation signatures that can denote the presence of certain cancers with 98.2% accuracy. 

DNA stores genetic information in sequences of four nucleotide bases: A (adenine), T (thymine), G (guanine) and C (cytosine). These bases can be modified through DNA methylation. There are millions of DNA methylation markers in every single cell, and they change in the early stages of cancer development.

One common characteristic of many cancers is an epigenetic phenomenon called aberrant DNA methylation. Modifications in DNA can influence gene expression and are observable in cancer cells. A methylation profile can differentiate tumor types and subtypes and changes in the process often come before malignancy appears. This renders methylation very useful in catching cancers while in the early stages. 

However, deciphering slight changes in methylation patterns can be extremely difficult. According to the scientists, “identifying the specific DNA methylation signatures indicative of different cancer types is akin to searching for a needle in a haystack.”

Nevertheless, the researchers believe identifying these changes could become a useful biomarker for early detection of cancers, which is why they built their AI models.

The UK researcher team published its findings in the Oxford journal Biology Methods and Protocols titled, “Early Detection and Diagnosis of Cancer with Interpretable Machine Learning to Uncover Cancer-specific DNA Methylation Patterns.”

“Computational methods such as this model, through better training on more varied data and rigorous testing in the clinic, will eventually provide AI models that can help doctors with early detection and screening of cancers,” said Shamith Samarajiwa, PhD (above), Senior Lecturer and Group Leader, Computational Biology and Genomic Data Science, Imperial College London, in a news release. “This will provide better patient outcomes.” With additional research, clinical laboratories and pathologists may soon have new cancer diagnostics based on these AI models. (Photo copyright: University of Cambridge.)

Understanding Underlying Mechanisms of Cancer

To perform their research, the UK team obtained methylation microarray data on 13 human cancer types and 15 non-cancer types from The Cancer Genome Atlas (TCGA) of the National Cancer Institute (NCI) Center for Cancer Genomics. The DNA fragments they examined came from tissue samples rather than blood-based samples. 

The researchers then used a combination of machine learning and deep learning techniques to train an AI algorithm to examine DNA methylation patterns of the collected data. The algorithm identified and differentiated specific cancer types, including breast, liver, lung and prostate, from non-cancerous tissue with a 98.2% accuracy rate. The team evaluated their AI model by comparing the results to independent research. 

In their Biology Methods and Protocols paper, the authors noted that their model does require further training and testing and stressed that “the important aspect of this study was the use of an explainable and interpretable core AI model.” They also claim their model could help medical professionals understand “the underlying mechanisms that contribute to the development of cancer.” 

Using AI to Lower Cancer Rates Worldwide

According to the Centers for Disease Control and Prevention (CDC), cancer ranks as the second leading cause of death in the United States with 608,371 deaths reported in 2022.  The leading cause of death in the US is heart disease with 702,880 deaths reported in the same year. 

Globally cancer diagnoses and death rates are even more alarming. World Health Organization (WHO) data shows an estimated 20 million new cancer cases worldwide in 2022, with 9.7 million persons perishing from various cancers that year.

The UK researchers are hopeful their new AI model will help lower those numbers. They state in their paper that “most cancers are treatable and curable if detected early enough.”

More research and studies are needed to confirm the results of this study, but it appears to be a very promising line of exploration and development of using AI to detect, identify, and diagnose cancer earlier. This type of probing could provide pathologists with improved tools for determining the presence of cancer and lead to better patient outcomes. 

—JP Schlingman

Related Information:

New AI Detects 13 Deadly Cancers with 98% Accuracy from Tissue Samples

Will it Soon Be Possible for Doctors to Use AI to Detect and Diagnose Cancer?

Early Detection and Diagnosis of Cancer with Interpretable Machine Learning to Uncover Cancer-specific DNA Methylation Patterns

Study Suggests AI May Soon Be Able to Detect Cancer

AI Analyzes DNA Methylation for Early Cancer Detection

Aberrant DNA Methylation as a Cancer-Inducing Mechanism

Global Cancer Burden Growing, Amidst Mounting Need for Services

Aberrant DNA Methylation as a Cancer-inducing Mechanism

University College London Researchers Develop Carbon Beads That Slow the Progress of Liver Disease and Improve Gut Microbiome

As this therapeutic approach gains regulatory approval, clinical laboratory tests to determine condition of patient’s gut microbiota and monitor therapy will be needed

Some developments in the clinical laboratory industry are less about diagnostic tests and more about novel approaches to therapy. Such is the case with a new carbon bead technology developed by researchers from University College London (UCL) and the Royal Free Hospital intended to remove harmful bacteria toxins from the gut before they leak to the liver. The macroporous beads, which come in small pouches, are delivered orally and could be utilized in the future to treat a number of diseases.

Why is this relevant? Once a new treatment is accepted for clinical use, demand increases for a clinical laboratory test that confirms the therapy will likely work and to monitor its progress.

In collaboration with Yaqrit, a UK-based life sciences company that develops treatments for chronic liver disease, the UCL and Royal Free Hospital scientists engineered the carbon beads—known as CARBALIVE—to help restore gut health. They measured the technology’s impact on liver, kidney, and brain function in both rats and mice.

“The influence of the gut microbiome on health is only just beginning to be fully appreciated,” said Rajiv Jalan, PhD, Professor of Hepatology at UCL in a press release. “When the balance of the microbiome is upset, ‘bad’ bacteria can proliferate and out-compete the ‘good’ bacteria that keeps the gut healthy.

“One of the ways [the ‘bad’ bacteria] do this is by excreting endotoxin, toxic metabolites, and cytokines that transform the gut environment to make it more favorable to them and hostile to good bacteria,” he continued. “These substances, particularly endotoxin, can trigger gut inflammation and increase the leakiness of the gut wall, resulting in damage to other organs such as the liver, kidneys, and brain.”

The researchers published their findings in Gut, a journal of the British Society of Gastroenterology, titled, “Clinical, Experimental and Pathophysiological Effects of Yaq-001: A Non-absorbable, Gut-restricted Adsorbent in Models and Patients with Cirrhosis.”

“I have high hopes that the positive impact of these carbon beads in animal models will be seen in humans, which is exciting not just for the treatment of liver disease but potentially any health condition that is caused or exacerbated by a gut microbiome that doesn’t work as it should,” said Rajiv Jalan, PhD (above), Professor of Hepatology, University College London, in a press release. “This might include conditions such as irritable bowel syndrome (IBS), for example, which is on the rise in many countries.” Though not a clinical laboratory diagnostic test, new therapies like CARBALIVE could be a boon to physicians treating patients with IBS and other gastrointestinal conditions.

Developing the Carbon Beads

The team discovered CARBALIVE is effective in the prevention of liver scarring and injury in animals with cirrhosis when ingested daily for several weeks. They also found a reduced mortality rate in test animals with acute-on-chronic-liver-failure (ACLF).

After achieving success with CARBALIVE in animals, the researchers tested the technology on 28 cirrhosis patients. The carbon beads proved to be safe for humans and had inconsequential side effects.

“In cirrhosis, a condition characterized by scarring of the liver, it is known that inflammation caused by endotoxins can exacerbate liver damage,” Jalan explained. “Part of the standard treatment for cirrhosis is antibiotics aimed at controlling bad bacteria, but this comes with the risk of antibiotic resistance and is only used in late-stage disease.”

The beads, which are smaller than a grain of salt, contain an exclusive physical structure that absorbs large and small molecules in the gut. They are intended to be taken with water at bedtime as harmful bacteria is more likely to circulate through the body at night which could result in damage. The carbon beads do not kill bacteria, which decreases the risk of antibiotic resistance. They eventually pass through the body as waste.

“They work by absorbing the endotoxins and other metabolites produced by ‘bad’ bacteria in the gut, creating a better environment for the good bacteria to flourish and helping to restore microbiome health,” said Michal Kowalski, M.Sc.Eng, Director and VP of Operations at Yaqrit, in the UCL news release.

“This prevents these toxins from leaching into other areas of the body and causing damage, as they do in cirrhosis,” he added. “The results in animal models are very positive, with reduction in gut permeability, liver injury, as well as brain and kidney dysfunction.”

Additional Research

The researchers plan to perform further clinical trials in humans to determine if the carbon beads are effective at slowing the progression of liver disease. If the benefits that were observed in lab animals prove to be compelling in humans, the technology may become an invaluable tool for the treatment of liver disease and other diseases associated with poor microbiome health in the future.

According to the American Liver Foundation, 4.5 million adults in the US have been diagnosed with liver disease. However, it is estimated that 80 to 100 million adults have some form of fatty liver disease and are unaware of it. Liver disease was the 12th leading cause of death in the US in 2020 with 51,642 adults perishing from the disease that year.

According to BMC Public Health, globally there were 2.05 million new cases of liver cirrhosis diagnosed in 2019. In that year, 1.47 million people around the world died from the disease.

More research and clinical studies are needed before this novel technology can be used clinically. When and if that happens, the demand for clinical laboratory tests that measure microbiome deficiencies and monitor patient progress during therapy will likely be high.

—JP Schlingman

Related Information:

Carbon Beads Help Restore Healthy Gut Microbiome and Reduce Liver Disease Progression

Clinical, Experimental and Pathophysiological Effects of Yaq-001: A Non-absorbable, Gut-restricted Adsorbent in Models and Patients with Cirrhosis

Tiny Beads of Carbon Could Save Lives

UCL Study Reveals Carbon Beads Could Help Reduce Progression of Liver Disease

How Many People Have Liver Disease?

Global Epidemiology of Cirrhosis—Aetiology, Trends and Predictions

Global Burden of Liver Cirrhosis and Other Chronic Liver Diseases Caused by Specific Etiologies from 1990 to 2019

Acute-on-Chronic Liver Failure: Definition, Prognosis and Management

At-Home Paper Influenza Test Differentiates Strains, Gives Hope for Improved Screening and Surveillance of Viral Outbreaks

Researchers used CRISPR-based assays to develop new clinical laboratory point-of-care blood test which boasts accuracy, affordability, and accessibility

Here’s a novel use of paper as clinical laboratory test media. Researchers at Princeton University in New Jersey, the Massachusetts Institute of Technology’s Broad Institute, and Harvard University have developed an at-home paper-strip test that can not only identify the presence of influenza, but it can also differentiate between different strains of the flu bug.

According to UPI, the test can “distinguish between influenza A and influenza B—the two main types of seasonal flu—as well as identifying more virulent strains like H1N1 and H3N2.”

Many research teams are working to develop paper-based diagnostic screening tests because of their lower cost to produce and usefulness in remote locations. Should this near-patient point-of-care test become clinically viable, it could mean shorter times to answer, enabling speedier diagnoses and earlier start of treatment.

It also means patient specimens do not have to be transported to a clinical laboratory for testing. And reduced cost per test makes it possible to test more people. This serves the public health aspect of monitoring outbreaks of influenza and other diseases and gives hope for improved treatment outcomes.

“Being able to tease apart what strain or subtype of influenza is infecting a patient has repercussions both for treating them and public health interventions, said Jon Arizti Sanz, PhD, co-lead study author and postdoctoral researcher at the Broad Institute of Harvard and MIT, in a Broad Institute news release.

The researchers published their findings in The Journal of Molecular Diagnostics titled, “CRISPR-Based Assays for Point-of-Need Detection and Subtyping of Influenza.”

“Ultimately, we hope these tests will be as simple as rapid antigen tests, and they’ll still have the specificity and performance of a nucleic acid test that would normally be done in a laboratory setting,” Cameron A. Myhrvold, PhD (above), Assistant Professor of Molecular Biology at Princeton University in New Jersey, told CIDRAP. Influenza tests that can be performed at the point of care and in remote locations may reduce the number of screening tests performed by clinical laboratories. (Photo copyright: Michael James Butts/Hertz Foundation.)

Inspiration from Prior COVID-19 Test

According to an article published by the Center for Infectious Disease Research and Policy Research and Innovation Office (CIDRAP) at the University of Minnesota, the original test was developed in 2020 in a Harvard laboratory led by computational geneticist Pardis Christine Sabeti, MD, PhD, professor, Department of Organismic and Evolutionary Biology, and co-senior author of the study.

Her team developed their tests using Streamlined Highlighting of Infections to Navigate Epidemics (SHINE), “a clustered regularly interspaced short palindromic repeats (CRISPR)-based RNA detection platform,” the researchers wrote in their Journal of Molecular Diagnostics paper.

“SHINE has a runtime of 90 minutes, can be used at room temperature and only requires an inexpensive heat block to heat the reaction. The SHINE technology has previously been used to identify SARS-CoV-2 and later to distinguish between the Delta and Omicron variants,” Bioanalysis Zone reported.

“The test uses genetically engineered enzymes to identify specific sequences of viral RNA in samples,” the researchers told UPI. Originally designed to detect COVID-19, the team adapted the technology to detect influenza in 2022 “with the aim of creating a screening tool that could be used in the field or in clinics rather than hospitals or high-tech diagnostic labs,” they said.

Influenza A and B as well as H1N1 and H3N2 subtypes were the targets of the four SHINE assays. “When tested on clinical samples, these optimized assays achieved 100% concordance with quantitative RT-PCR. Duplex Cas12a/Cas13a SHINE assays were also developed to detect two targets simultaneously,” the researchers wrote in their paper.

The team used “20 nasal swabs from people with flu-like symptoms during the 2020-2021 flu season, nasal fluid from healthy people as the control, and 2016-2021 influenza sequences downloaded from the National Center for Biotechnology Information Influenza (NICB) database. They compared the results with those from quantitative reverse transcription-polymerase chain reaction (RT-PCR) tests,” CIDRAP reported.

The original 2020 test (shown above) takes 90 minutes to develop at room temperature. The test developers aim to drop this down to 15 minutes. In comparison, typical polymerase chain reaction (PCR) testing requires medical laboratories to have specialized equipment, trained staff, and prolonged processing times, the Broad Institute news release notes. (Photo copyright: Broad Institute.)

Implications of the New Tests

The ease of the new tests is an important development since approximately only 1% of individuals who come down with the flu see doctors for testing, according to the news release. And researchers had this in mind, looking at speed, accuracy, and affordability as a means to “improve outbreak response and infection care around the world,” UPI reported.

There are great benefits to strain differentiation that be achieved with the new test. Doctors are hopeful the test will help dial in the best treatment plans for patients since some strains are resistant to the antiviral medication oseltamivir (Tamiflu), UPI noted. This is significant since Tamiflu “is a common antiviral,” said Sanz in the Broad Institute news release.

“These assays have the potential to expand influenza detection outside of clinical laboratories for enhanced influenza diagnosis and surveillance,” the Journal of Molecular Diagnostics paper noted. This allows for more strategic treatment planning.

“Using a paper strip readout instead of expensive fluorescence machinery is a big advancement, not only in terms of clinical care but also for epidemiological surveillance purposes,” said Ben Zhang, an MD candidate in the Health Sciences and Technology at Harvard and co-first author of the study, in the Broad Institute news release.

Future Plans for Tests

“With further development, the test strip could be reprogrammed to distinguish between SARS-CoV-2 and flu and recognize swine flu and avian flu, including the H5N1 subtype currently causing an outbreak in US dairy cattle,” the study authors told CIDRAP.

The team is also looking at ways to help prevent H5N1 from crossing into human contamination, Sanz told UPI.

The new Princeton/MIT/Harvard tests echo the trend to bring in affordability and ease-of-use with accurate results as an end goal. Faster results mean the best treatments for each person can start sooner and may render the transport of specimens to a clinical laboratory as a second step unnecessary.

As research teams work to develop paper-based viral tests for their plethora of benefits, clinical laboratories will want to pay close attention to this development as it can have a big implication on assisting with future outbreaks.

Additional research is needed before these tests are going to be commonplace in homes worldwide, but this first step brings inspiration and hope of what’s to come. 

—Kristin Althea O’Connor

Related Information:

Simple Test for Flu Could Improve Diagnosis and Surveillance

Simple Paper-Strip Test Might Spot Flu, Identify Strain

CRISPR-Based Assays for Point-of-Need Detection and Subtyping of Influenza

Paper Strip Test Can Identify Flu Subtypes, May Have Other Applications, Scientists Say

Streamlined Inactivation, Amplification, and Cas13-based Detection of SARS-Cov-2

Paper Strip Test Using CRISPR and SHINE Technology Has Been Developed for Rapid Influenza Diagnosis

Researchers in China Develop AI-powered Tool That Can Diagnose Three Cancers Using a Drop of Dried Blood

Use of artificial intelligence in clinical laboratory testing could improve the diagnosis of cancer worldwide

In a proof of concept study, scientists at Shanghai Jiao Tong University in China have developed a clinical laboratory test that utilizes artificial intelligence (AI) to diagnose three types of cancer from a single drop of dried blood. The paper-based test was able to identify patients with colorectal, gastric, and pancreatic cancers and distinguish between patients with and without cancer.

The team’s goal was to develop a way to diagnose cancer while the disease is still in the earlier stages, especially in rural areas.

“Over a billion people across the world experience a high rate of missed disease diagnosis, an issue that highlights the need for diagnostic tools showing increased accuracy and affordability. In addition, such tools could be used in ecologically fragile and energy-limited regions, pointing to the need for developing solutions that can maximize health gains under limited resources for enhanced sustainability,” the researchers wrote in an article published in the journal Nature Sustainability titled, “A Sustainable Approach to Universal Metabolic Cancer Diagnosis.”

The researchers determined that by using less than 0.05 millimeters of dried blood, their test could accurately and quickly identify if a patient had cancer between 82% to 100% of the time.

According to Chaoyuan Kuang, MD, PhD (above), an oncologist at Montefiore Health System and assistant professor at the Albert Einstein College of Medicine, unlike liquid blood, dried serum can be “collected, stored, and transported at much lower cost and with much simpler equipment,” Live Science reported. “This could help democratize the availability of cancer early detection testing across the world,” he added. A paper-based clinical laboratory test that can detect and distinguish one cancer type from another would be a boon to cancer diagnosis worldwide. (Photo copyright: Albert Einstein College of Medicine.)

Improving Cancer Screening in Rural Areas

An earlier study conducted in China in 2022 examined results from 1,570 cancer survivors from both urban and rural areas of China. That study showed that 84.1% of the patients were diagnosed with cancer only after developing symptoms and that urban patients were more likely to be diagnosed in the early stages of cancer. In addition, rural patients also had less screening and treatment options available to them.

The researchers in this latest Chinese study tested their AI model on blood donors with and without cancer and compared the results to traditional liquid-blood biopsy tests.

“Based on modeling they performed, they reported the new tool could reduce the estimated proportion of undiagnosed cases of pancreatic, gastric, and colorectal cancers by about 20% to 50% if it was used for population-level cancer screening in rural China,” Live Science reported. 

The scientists used dried serum spots (DSS) and machine learning to perform the research. According to their Nature Sustainability paper, DSS can be challenging in cancer research because sensitive biomarkers in the samples are often degraded or have inadequate amount of blood for proper analysis. To circumvent these issues, the researchers used nanoparticle-enhanced laser desorption/ionization mass spectrometry (NPELDI MS) to increase reliability and sensitivity. Inorganic nanoparticles were applied to the samples to strengthen selectivity and refine metabolic compounds from the samples.

However, the study authors noted that “the adaptation of NPELDI MS to dried spot analysis has not been validated,” Interesting Engineering reported.

A ‘Great Start’

The machine learning algorithm the Chinese scientists created demonstrates that DSS samples can be used to preserve important biological markers and could be beneficial in the diagnosis of cancer. 

Their research indicated an overall reduction rate of undiagnosed cancers in the range of 20.35% to 55.10%. The researchers estimated the implementation of their AI tool could reduce the proportion of specific undiagnosed cancer cases in rural China by:

  • 84.30% to 29.20% for colorectal cancer,
  • 77.57% to 57.22% for gastric cancer, and
  • 34.56% to 9.30% for pancreatic cancer.

It’s a “great start,” Chaoyuan Kuang, MD, PhD, an oncologist at Montefiore Health System and assistant professor at the Albert Einstein College of Medicine told Live Science. “This cancer test won’t enter use for a long time,” he said. Nevertheless, the potential of the tool is “immense,” he added, but that “we are still years away from being able to offer this test to patients. 

“With further development, it could theoretically be used for the early detection of other types of cancer or for other diseases, or to monitor the progression of disease in patients who have already been diagnosed,” he noted.

Further research and clinical trials are needed before this AI tool can be used in a clinical diagnostic setting. This study is another example of researchers looking for cancer biomarkers in specimen types that are not tissue and further supports the hope that machine learning may one day detect cancer in earlier stages, increase survival rates, and save healthcare costs.

One factor motivating this type of research in China is the fact that the nation has more than 36,000 hospitals and approximately 20,000 anatomic pathologists. Of this total, only a minority of these pathologists have been trained to the standards of North America and Northern Europe.

Like other nations, China’s demand for subspecialist pathology services outstrips its supply of such pathologists. This is the reason why researchers in that country want to develop diagnostic assays for cancer and other diseases that are faster, cheaper, and comparable to a human pathologist in accuracy.

—JP Schlingman

Related Information:

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A Sustainable Approach to Universal Metabolic Cancer Diagnosis

New Sustainable Diagnostic Approach Offers Precision Cancer Testing with Minimal Environmental Impact

The Urban-Rural Disparities and Associated Factors of Health Care Utilization Among Cancer Patients in China

University Hospitals Birmingham Claims Its New AI Model Detects Certain Skin Cancers with Nearly 100% Accuracy

UK Study Claims AI Reading of CT Scans Almost Twice as Accurate at Grading Some Cancers as Clinical Laboratory Testing of Sarcoma Biopsies

UK’s National Health Service Tests AI Tool That Can Spot Cancer in Mammograms Missed by Doctors

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