Author Interviews, Cancer Research, Microbiome / 07.03.2024
Sanger Institute Developing Microbiome-Based Biomarkers To Predict Response to Cancer Immunotherapy
MedicalResearch.com Interview with:
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Dr. Gunjur[/caption]
Dr Ashray Gunjur
MBBS (Hons), B. Med Sci, MPHTM FRACP
Clinical Research Training Fellow
Melbourne, Australia
MedicalResearch.com: What is the background for this study?
Response: As background, the last ~5 years have seen a surge of interest in the relationship between gut microbiota and cancer response to immune checkpoint blockade (ICB). We know that though a fraction of many different cancer types will respond to these therapies, it is currently very hard to predict who that will be- so ‘microbiome’ based biomarkers to select patients, or even strategies to change a patient’s microbiome to enhance their chance of responding, are very attractive.
A key challenge, however, has been a lack of consistency in the microbes associated with response or non-response across different studies from different regions. While geographic, methodological, and technical variation likely contribute to this, most studies examined the gut microbiome at a genus- or species- taxonomic rank level, while we know there is significant intra-species (strain-level) diversity. As such, one of our key research questions was whether we could improve the reproducibility of microbial ‘signatures’ of response across cohorts using higher resolution approaches- with our hypothesis being that strain-resolution signatures would outperform species- or lower resolution signatures.
We obtained our signature by analysing baseline faecal samples from the CA209-538 clinical trial, a wonderful investigator-initiated study sponsored by the Olivia Newton-John Cancer Research Institute (Melbourne, Australia). I was fortunate enough to work on this trial as a clinical investigator while training to be a medical oncologist.
Dr. Gunjur[/caption]
Dr Ashray Gunjur
MBBS (Hons), B. Med Sci, MPHTM FRACP
Clinical Research Training Fellow
Melbourne, Australia
MedicalResearch.com: What is the background for this study?
Response: As background, the last ~5 years have seen a surge of interest in the relationship between gut microbiota and cancer response to immune checkpoint blockade (ICB). We know that though a fraction of many different cancer types will respond to these therapies, it is currently very hard to predict who that will be- so ‘microbiome’ based biomarkers to select patients, or even strategies to change a patient’s microbiome to enhance their chance of responding, are very attractive.
A key challenge, however, has been a lack of consistency in the microbes associated with response or non-response across different studies from different regions. While geographic, methodological, and technical variation likely contribute to this, most studies examined the gut microbiome at a genus- or species- taxonomic rank level, while we know there is significant intra-species (strain-level) diversity. As such, one of our key research questions was whether we could improve the reproducibility of microbial ‘signatures’ of response across cohorts using higher resolution approaches- with our hypothesis being that strain-resolution signatures would outperform species- or lower resolution signatures.
We obtained our signature by analysing baseline faecal samples from the CA209-538 clinical trial, a wonderful investigator-initiated study sponsored by the Olivia Newton-John Cancer Research Institute (Melbourne, Australia). I was fortunate enough to work on this trial as a clinical investigator while training to be a medical oncologist.
Wilson N. Merrell
Ph.D. Student
Dr. Di Ciano[/caption]
Patricia Di Ciano, PhD
Lauren C. Davis, MBS
Department of Medical Education
Geisinger Commonwealth School of Medicine
Scranton, PA 19409
MedicalResearch.com: What is the background for this study?
Response: Financial conflicts of interest (COIs) resulting from ties between academia and industry have been under scrutiny for their potential to hinder the integrity of medical research. COIs can lead to implicit bias, compromise the research process, and erode public trust (1-6). The American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders (DSM), standardizes symptom criteria and codifies psychiatric disorders. This manual contributes to the approval of new drugs, extensions of patent exclusivity, and can influence payers and mental health professionals seeking third-party reimbursements. Given the implications of the DSM on public health, it is paramount that it is free of industry influence. Previous research has shown a high prevalence of industry ties among panel and task force members of the DSM-IV-TR and DSM-5, despite the implementation of a disclosure policy for the DSM-5 (7,8). This study (9) determined the extent and type of COIs received by panel and task-force members of the DSM-5-TR (2022) (10). As the DSM-5-TR did not disclose COI, we used the Center for Medicare and Medicaid Services Open Payments (OP) database (11) to quantify them.
Kalli Koukounas[/caption]
Kalli Koukounas, MPH
Dr. Lu Qi[/caption]
Lu Qi, MD, PhD, FAHA
Interim Chair, Department of Epidemiolog
HCA Regents Distinguished Chair and Professor
Tulane University School of Public Health and Tropical Medicine
Director, Tulane University Obesity Research Center
Director, Tulane Personalized Health Institute
New Orleans, LA 70112
MedicalResearch.com: What is the background for this study?
Response: Adding salt to foods is a behavior reflecting long-term preference to salty diets. High sodium intake is a major risk factor for chronic kidney disease.
In our previous studies, we have found that adding salt to foods at the table is related to various disorders including cardiovascular diseases, diabetes, and mortality.
Dr. Angélica Cifuentes Kottkamp[/caption]
Angélica
Prof. Rong Xu[/caption]
Rong Xu, PhD
Dr. Davaasambuu[/caption]
Dr Ganmaa Davaasambuu MD PhD
Associate Professor
Harvard T.H. Chan School of Public Health
MedicalResearch.com: What is the background for this study?
Response: The crucial role of vitamin D in facilitating calcium absorption from the diet and promoting calcium deposition in bones (known as 'mineralization') has been a long-established understanding. Furthermore, some observational studies have reported an association between low vitamin D levels and a heightened risk of bone fractures in children. This raised the possibility that vitamin D supplements could potentially play a role in decreasing fracture risk in children with initially low baseline levels. However, clinical trials assessing the causal link between low vitamin D status and reduced fracture risk were necessary, and such trials had not been conducted before.
Dr. Dolatshahi[/caption]
Mahsa Dolatshahi, M.D., M.P.H.
Post-doctoral research fellow
Mallinckrodt Institute of Radiology (MIR)
Washington University School of Medicine
St. Louis
MedicalResearch.com: What is the background for this study?
Response: Obesity at midlife is recognized as a risk factor for developing Alzheimer disease decades afterwards. However, body mass index on its own does not adequately represent the risks associated with obesity.
In this study, we went beyond BMI and considered anatomical distribution of body fat, including the metabolically active visceral fat in the belly, and showed its association with Alzheimer pathology in the form of amyloid proteins. In addition, visceral fat along with obesity and insulin resistance were associated with thinning of brain cortex, as early as midlife.
Dr. Mohyuddin[/caption]
Hira Mohyuddin, PGY-2
Psychiatry Residency Training Program
The George Washington University
MedicalResearch.com: What is the background for this study?
Response: Frailty has become increasingly significant as the global population grows older, as this syndrome is linked with a higher mortality and morbidity in aging. Causes contributing to frailty are poorly understood, but it seems that the role of inflammation is very likely.
While other chronic infections were shown to precipitate and perpetuate inflammation that contributes to the development of frailty, no prior study has previously focused on possible links between Toxoplasma gondii and geriatric frailty. Benefiting from a collaboration with Spanish and Portuguese researchers, we have now tested, for the first time to our knowledge, this possible association.
Dr. Traverso[/caption]
Giovanni Traverso MD PhD
Karl Van Tassel (1925) Career Development Professor
Department of Mechanical Engineering
Koch Institute of Integrative Cancer Research
Division of Gastroenterology
Brigham and Women’s Hospital
Harvard Medical School, Boston, MA, USA
MedicalResearch.com: What is the background for this study?
Response: I think its always important to acknowledge that this is a big team effort. We have the teams from MIT, Celero Systems, West Virgnia University (WVU) and Brigham and Women’s Hospital (BWH) all working together on this. For this study, Celero prototyped the devices that we tested in pre-clinical (Swine) models and in a first-in-human study with the team at WVU.
Our lab focuses on the development of ingestible devices for drug delivery and sensing and these have informed the development of these efforts as you can see.
Lisa-Marie Smale, PharmD
Dr. Minneci[/caption]
Peter C. Minneci, MD
Chair of Surgery at Nemours Children’s Health
Delaware Valley
MedicalResearch.com: What is the background for this study? Would you briefly explain the symptoms/course of pilonidal disease?
Response: Pilonidal disease is relatively common and affects up to 1% of the population starting in adolescence and up until young adulthood. Pilonidal disease occurs when cysts or sinuses form between the buttocks. It is believed to be an inflammatory reaction to hair or debris that gets caught in the crease of the buttocks. Risk factors for the condition include a sedentary lifestyle, hygiene and obesity.
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Pilonidal Cyst