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.
“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.
“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.”
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.”
Few anatomical tools hold more potential to revolutionize the science of diagnostics than biomarkers, and pathologists and medical laboratories will be first in line to put these powerful tools to use helping patients with chronic diseases
There’s good news for both anatomic pathology laboratories and medical laboratories worldwide. Large numbers of clinically-useful new biomarkers continue to be validated and are in development for use in diagnostic tests and therapeutic drugs.
Clinical laboratories rely on biomarkers for pathology tests and procedures that track and identify infections and disease during the diagnostic process. Thus, trends that highlight the critical role biomarkers play in medical research are particularly relevant to pathology groups and medical laboratories.
Here’s an overview of critical trends in biomarker research and development that promise to improve diagnosis and treatment of chronic disease.
Emerging Use of Predictive Biomarkers in Precision Medicine
PM involves an approach to healthcare that is fine-tuned to each patient’s unique condition and physiology. As opposed to the conventional one-size-fits-all approach, which looks at the best options for the average person without examining variations in individual patients.
Predictive biomarkers identify individuals who will most likely respond either favorably or unfavorably to a drug or course of treatment. This improves a patient’s chance to receive benefit or avoid harm and goes to the root of Precision Medicine. (Image copyright: Pennside Partners.)
The National Institutes of Health (NIH) defines PM as “an emerging approach for disease treatment and prevention that considers individual variability in genes, environment, and lifestyle for each person.” It gives physicians and researchers the ability to more accurately forecast which prevention tactics and treatments will be optimal for certain patients.
Combining Drugs for Specific Outcomes
Cancer treatment will be complimented by the utilization of combination drugs that include two or more active pharmaceutical ingredients. Many drug trials are currently being performed to determine which combination of drugs will be the most favorable for specific cancers.
Combination drugs should become crucial in the treatment of different cancers treatments, such as immunotherapy, which involves treating disease by inducing, enhancing, or suppressing an immune response.
Biomarkers associated with certain cancers may enable physicians and researchers to determine which combination drugs will work best for each individual patient.
Developing More Effective Diagnostics
In Vitro diagnostics (IVDs) are poised for massive growth in market share. A report by Allied Market Research, states the worldwide IVD market will reach $81.3 billion by 2022. It noted that IVD techniques in which bodily fluids, such as blood, urine, stool, and sputum are tested to detect disease, conditions, and infections include important technologies such as:
Allied Market Research expects growth of the IVD market to result from these factors:
Increases in chronic and infectious diseases;
An aging population;
Growing knowledge of rare diseases; and
Increasing use of personalized medicines.
The capability to sequence the human genome is further adding to improvements in diagnostic development. Pharmaceutical companies can generate diagnostic counterparts alongside related drugs.
Biopsies from Fluid Sources
Millions of dollars have been spent on developing liquid biopsies that detect cancer from simple blood draws. The National Cancer Institute Dictionary of Cancer Terms defines a liquid biopsy as “a test done on a sample of blood to look for cancer cells from a tumor that are circulating in the blood or for pieces of DNA from tumor cells that are in the blood.”
At present, liquid biopsies are typically used only in the treatment and monitoring of cancers already diagnosed. Companies such as Grail, a spinoff of Illumina, and Guardant Health are striving to develop ways to make liquid biopsies a crucial part of cancer detection in the early stages, increasing long-term survival rates.
“The holy grail in oncology has been the search for biomarkers that could reliably signal the presence of cancer at an early stage,” said Dr. Richard Klausner, Senior Vice President and Chief Medical Officer at Grail.
Grail hopes to market a pan-cancer screening test that will measure circulating nucleic acids in the blood to detect the presence of cancer in patients who are experiencing no symptoms of the disease.
Clinical Trials and Precision Medicine
The Precision Medicine Initiative (PMI), launched by the federal government in 2015, investigates ways to create tailor-made treatments and prevention strategies for patients based on their distinctive attributes.
Two ongoing studies involved in PMI research are MATCH and TAPUR:
MATCH (Molecular Analysis for Therapy Choice) is a clinical trial run by The National Cancer Institute. The researchers are studying tumors to learn if they possess gene abnormalities that are treatable by known drugs.
TAPUR (Targeted Agent and Profiling Utilization Registry), is a non-randomized clinical trial being conducted by the American Society of Clinical Oncology (ASCO). The researchers are chronicling the safety and efficacy of available cancer drugs currently on the market.
New Tools for Pathologists and Clinical Laboratories
The attention and funds given to these types of projects expand the possibilities of being able to develop targeted therapies and treatments for patients. Such technological advancements could someday enable physicians to view and treat cancer as a product of specific gene mutations and not just a disease.
These trends will be crucial and favorable for clinical laboratories in the future. As tests and treatments become unique to individual patients, pathologists and clinical laboratories will be on the frontlines of providing advanced services to healthcare professionals.
