scholarly journals What Is Known about Theragnostic Strategies in Colorectal Cancer

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 140
Author(s):  
Alessandro Parisi ◽  
Giampiero Porzio ◽  
Fanny Pulcini ◽  
Katia Cannita ◽  
Corrado Ficorella ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Gut Microbiota ◽  
Liquid Biopsy ◽  
Clinical Evidence ◽  
Inflammatory Responses ◽  
Residual Disease ◽  
Fecal Microbiota Transplantation ◽  
Checkpoint Inhibitors ◽  
Systemic Treatments ◽  
Metastatic Setting

Despite the paradigmatic shift occurred in recent years for defined molecular subtypes in the metastatic setting treatment, colorectal cancer (CRC) still remains an incurable disease in most of the cases. Therefore, there is an urgent need for new tools and biomarkers for both early tumor diagnosis and to improve personalized treatment. Thus, liquid biopsy has emerged as a minimally invasive tool that is capable of detecting genomic alterations from primary or metastatic tumors, allowing the prognostic stratification of patients, the detection of the minimal residual disease after surgical or systemic treatments, the monitoring of therapeutic response, and the development of resistance, establishing an opportunity for early intervention before imaging detection or worsening of clinical symptoms. On the other hand, preclinical and clinical evidence demonstrated the role of gut microbiota dysbiosis in promoting inflammatory responses and cancer initiation. Altered gut microbiota is associated with resistance to chemo drugs and immune checkpoint inhibitors, whereas the use of microbe-targeted therapies including antibiotics, pre-probiotics, and fecal microbiota transplantation can restore response to anticancer drugs, promote immune response, and therefore support current treatment strategies in CRC. In this review, we aim to summarize preclinical and clinical evidence for the utilization of liquid biopsy and gut microbiota in CRC.

scholarly journals Gut Microbiota Manipulation as a Tool for Colorectal Cancer Management: Recent Advances in Its Use for Therapeutic Purposes

2020 ◽  
Vol 21 (15) ◽  
pp. 5389
Author(s):  
Federica Perillo ◽  
Chiara Amoroso ◽  
Francesco Strati ◽  
Maria Rita Giuffrè ◽  
Angélica Díaz-Basabe ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Gut Microbiota ◽  
Targeted Therapies ◽  
Inflammatory Responses ◽  
Fecal Microbiota Transplantation ◽  
Large Body ◽  
Cancer Recurrence ◽  
Fecal Microbiota ◽  
Cancer Management ◽  
Host Microbe Interactions

Colorectal cancer (CRC) is a multifaceted disease influenced by both environmental and genetic factors. A large body of literature has demonstrated the role of gut microbes in promoting inflammatory responses, creating a suitable microenvironment for the development of skewed interactions between the host and the gut microbiota and cancer initiation. Even if surgery is the primary therapeutic strategy, patients with advanced disease or cancer recurrence after surgery remain difficult to cure. Therefore, the gut microbiota has been proposed as a novel therapeutic target in light of recent promising data in which it seems to modulate the response to cancer immunotherapy. The use of microbe-targeted therapies, including antibiotics, prebiotics, live biotherapeutics, and fecal microbiota transplantation, is therefore considered to support current therapies in CRC management. In this review, we will discuss the importance of host−microbe interactions in CRC and how promoting homeostatic immune responses through microbe-targeted therapies may be useful in preventing/treating CRC development.

scholarly journals Interplay between the Gut Microbiota and Inflammatory Mediators in the Development of Colorectal Cancer

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 734
Author(s):  
Gwangbeom Heo ◽  
Yunna Lee ◽  
Eunok Im
Keyword(s):  
Colorectal Cancer ◽  
Gut Microbiota ◽  
Inflammatory Mediators ◽  
Tumor Metastasis ◽  
Intestinal Tract ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Therapeutic Interventions ◽  
Potential Therapeutic Target ◽  
Necrosis Factor

Inflammatory mediators modulate inflammatory pathways during the development of colorectal cancer. Inflammatory mediators secreted by both immune and tumor cells can influence carcinogenesis, progression, and tumor metastasis. The gut microbiota, which colonize the entire intestinal tract, especially the colon, are closely linked to colorectal cancer through an association with inflammatory mediators such as tumor necrosis factor, nuclear factor kappa B, interleukins, and interferons. This association may be a potential therapeutic target, since therapeutic interventions targeting the gut microbiota have been actively investigated in both the laboratory and in clinics and include fecal microbiota transplantation and probiotics.

scholarly journals Crosstalk between Gut and Brain in Alzheimer’s Disease: The Role of Gut Microbiota Modulation Strategies

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 690
Author(s):  
Umair Shabbir ◽  
Muhammad Sajid Arshad ◽  
Aysha Sameen ◽  
Deog-Hwan Oh
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gut Microbiota ◽  
Dietary Habits ◽  
Inflammatory Responses ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Gut Dysbiosis ◽  
Dynamic Population

The gut microbiota (GM) represents a diverse and dynamic population of microorganisms and about 100 trillion symbiotic microbial cells that dwell in the gastrointestinal tract. Studies suggest that the GM can influence the health of the host, and several factors can modify the GM composition, such as diet, drug intake, lifestyle, and geographical locations. Gut dysbiosis can affect brain immune homeostasis through the microbiota–gut–brain axis and can play a key role in the pathogenesis of neurodegenerative diseases, including dementia and Alzheimer’s disease (AD). The relationship between gut dysbiosis and AD is still elusive, but emerging evidence suggests that it can enhance the secretion of lipopolysaccharides and amyloids that may disturb intestinal permeability and the blood–brain barrier. In addition, it can promote the hallmarks of AD, such as oxidative stress, neuroinflammation, amyloid-beta formation, insulin resistance, and ultimately the causation of neural death. Poor dietary habits and aging, along with inflammatory responses due to dysbiosis, may contribute to the pathogenesis of AD. Thus, GM modulation through diet, probiotics, or fecal microbiota transplantation could represent potential therapeutics in AD. In this review, we discuss the role of GM dysbiosis in AD and potential therapeutic strategies to modulate GM in AD.

Use of Circulating Cell-Free DNA to Guide Precision Medicine in Patients with Colorectal Cancer

2021 ◽  
Vol 72 (1) ◽  
pp. 399-413
Author(s):  
Van K. Morris ◽  
John H. Strickler
Keyword(s):  
Colorectal Cancer ◽  
Precision Medicine ◽  
Residual Disease ◽  
Cost Effective ◽  
Patient Specific ◽  
Blood Draw ◽  
Cell Free Dna ◽  
Free Dna ◽  
Metastatic Setting ◽  
Diagnostic Technology

Patient-specific biomarkers form the foundation of precision medicine strategies. To realize the promise of precision medicine in patients with colorectal cancer (CRC), access to cost-effective, convenient, and safe assays is critical. Improvements in diagnostic technology have enabled ultrasensitive and specific assays to identify cell-free DNA (cfDNA) from a routine blood draw. Clinicians are already employing these minimally invasive assays to identify drivers of therapeutic resistance and measure genomic heterogeneity, particularly when tumor tissue is difficult to access or serial sampling is necessary. As cfDNA diagnostic technology continues to improve, more innovative applications are anticipated. In this review, we focus on four clinical applications for cfDNA analysis in the management of CRC: detecting minimal residual disease, monitoring treatment response in the metastatic setting, identifying drivers of treatment sensitivity and resistance, and guiding therapeutic strategies to overcome resistance.

scholarly journals Gut Microbiota, Fusobacteria, and Colorectal Cancer

Diseases ◽  
2018 ◽  
Vol 6 (4) ◽  
pp. 109 ◽  
Author(s):  
Dervla Kelly ◽  
Liying Yang ◽  
Zhiheng Pei
Keyword(s):  
Colorectal Cancer ◽  
Gut Microbiota ◽  
Inflammatory Responses ◽  
Tumor Development ◽  
Host Responses ◽  
Future Research ◽  
Bacterial Microbiota ◽  
Promote Tumor Growth ◽  
Tumor Environment ◽  
Protective Strategies

The gut microbiota has emerged as an environmental contributor to colorectal cancer (CRC) in both animal models and human studies. It is now generally accepted that bacteria are ubiquitous colonizers of all exposed human body surfaces, including the entire alimentary tract (5). Recently, the concept that a normal bacterial microbiota is essential for the development of inflammation-induced carcinoma has emerged from studies of well-known colonic bacterial microbiota. This review explores the evidence for a role of fusobacteria, an anaerobic gram-negative bacterium that has repeatedly been detected at colorectal tumor sites in higher abundance than surrounding histologically normal tissue. Mechanistic studies provide insight on the interplay between fusobacteria, other gut microbiota, barrier functions, and host responses. Studies have shown that fusobacteria activate host inflammatory responses designed to protect against pathogens that promote tumor growth. We discuss how future research identifying the pathophysiology underlying fusobacteria colon colonization during colorectal cancer may lead to new therapeutic targets for cancer. Furthermore, disease-protective strategies suppressing tumor development by targeting the local tumor environment via bacteria represent another exciting avenue for researchers and are highlighted in this review.

scholarly journals Current Treatments of Metastatic Colorectal Cancer with Immune Checkpoint Inhibitors—2020 Update

2020 ◽  
Vol 9 (11) ◽  
pp. 3520
Author(s):  
Gerhard Jung ◽  
Daniel Benítez-Ribas ◽  
Ariadna Sánchez ◽  
Francesc Balaguer
Keyword(s):  
Colorectal Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Survival Rates ◽  
Clinical Trial Design ◽  
Predictive Biomarkers ◽  
Host Immune System ◽  
Systemic Treatments

During the last 20 years, chemotherapy has improved survival rates of colorectal cancer (CRC). However, the majority of metastatic cases do not respond to or progress after first line conventional chemotherapy and contribute to the fatalities of patients with CRC. Insights into the immune contexture of the tumor microenvironment (TME) have enabled the development of new systemic treatments that boost the host immune system against the tumor—the immune checkpoint inhibitors (ICI). These promising drugs have already shown astonishing efficacies in other cancer types and have raised new hope for the treatment of metastatic CRC (mCRC). In this review, we will summarize the results of the clinical trials that led to their accelerated approval by the U.S. Food and Drug Administration (FDA) in 2017, as well as all relevant recent studies conducted since then—some of which are not published yet. We will focus on therapeutic efficacy, but also discuss the available data for drug safety and security, changes in quality of life indicators and predictive biomarkers for treatment response. The burgeoning evidence for a potential use of ICIs in other settings than mCRC will also be mentioned. For each trial, we have made a preliminary assessment of the quality of clinical trial design and of the “European Society of Medical Oncology (ESMO) magnitude of clinical benefit” (ESMO-MCBS) in order to provide the first evidence-based recommendation to the reader.

scholarly journals 91P Liquid biopsy for detection of minimal residual disease after liver metastasectomy in stage IV colorectal cancer

2021 ◽  
Vol 32 ◽  
pp. S395-S396
Author(s):  
M.A. Gouda ◽  
M.J. Overman ◽  
H.J. Huang ◽  
J. Thomas ◽  
N.A. Dasari ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Minimal Residual Disease ◽  
Liquid Biopsy ◽  
Residual Disease ◽  
Stage Iv ◽  
Stage Iv Colorectal Cancer ◽  
Minimal Residual

scholarly journals The Role of Gut Microbiota in Lung Cancer: From Carcinogenesis to Immunotherapy

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiangjun Liu ◽  
Ye Cheng ◽  
Dan Zang ◽  
Min Zhang ◽  
Xiuhua Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Fecal Microbiota Transplantation ◽  
Checkpoint Inhibitors ◽  
Fecal Microbiota ◽  
Immune Homeostasis ◽  
Gut Dysbiosis ◽  
Underlying Mechanisms ◽  
And Function

The influence of microbiota on host health and disease has attracted adequate attention, and gut microbiota components and microbiota-derived metabolites affect host immune homeostasis locally and systematically. Some studies have found that gut dysbiosis, disturbance of the structure and function of the gut microbiome, disrupts pulmonary immune homeostasis, thus leading to increased disease susceptibility; the gut-lung axis is the primary cross-talk for this communication. Gut dysbiosis is involved in carcinogenesis and the progression of lung cancer through genotoxicity, systemic inflammation, and defective immunosurveillance. In addition, the gut microbiome harbors the potential to be a novel biomarker for predicting sensitivity and adverse reactions to immunotherapy in patients with lung cancer. Probiotics and fecal microbiota transplantation (FMT) can enhance the efficacy and depress the toxicity of immune checkpoint inhibitors by regulating the gut microbiota. Although current studies have found that gut microbiota closely participates in the development and immunotherapy of lung cancer, the mechanisms require further investigation. Therefore, this review aims to discuss the underlying mechanisms of gut microbiota influencing carcinogenesis and immunotherapy in lung cancer and to provide new strategies for governing gut microbiota to enhance the prevention and treatment of lung cancer.

scholarly journals The Association between Gut Microbiota and Intestinal Toll-like Receptors Genes Expression in Adenomatous and Colorectal Cancerous patients

2020 ◽  
Author(s):  
Sama Rezasoltani ◽  
Maryam Sharafkhah ◽  
Hamid Asadzadeh Aghdaei ◽  
Meysam Olfatifar ◽  
Ehsan Nazemalhosseini Mojarad ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Gut Microbiota ◽  
Intestinal Microbiota ◽  
Intestinal Inflammation ◽  
Inflammatory Responses ◽  
Bacteroides Fragilis ◽  
Normal Group ◽  
Adenomatous Polyposis ◽  
Toll Like Receptors ◽  
Genes Expression

Abstract Background: Toll-like receptor (TLR) signaling has been implicated in colorectal cancer (CRC) development. Intestinal microbiota can affect the expression of TLRs, which may induce inflammatory responses and impair the gut homeostasis. Here, we aimed to evaluate certain intestinal microbiota related to TLRs expression in colonic tissues of adenomatous polyposis and CRC patients. Results: Fecal and colonic tissue samples were collected from normal controls (NC), adenomatous (AP) cases and (CRC) patients via colonoscopy for CRC screening during 2016 to 2018. Fecal samples were collected to analyze intestinal bacteria including Streptococcus bovis , Enterococcus faecalis , Bacteroides fragilis , enterotoxigenic Bacteroides fragilis (ETBF) , Fusobacterium nucleatum , Porphyromonas gingivalis, Porphyromonas spp . and Roseburia spp . by real-time PCR. Gene expression of TLR2, TLR4 and TLR5 was examined in colonic tissues by qRT-PCR. Different abundant of gut bacteria were achieved in NC, AP and CRC groups. The genes expression of TLR2, TLR4 and TLR5 were significantly different in AP and CRC cases vs. normal group (P value <0.05). There was a significant relationship between TLR2, TLR4, TLR5 genes expression and Roseburia spp., P. gingivalis and ETBF quantity in normal group. Also significant association between TLR2, TLR4 genes expression levels and the quantity of S.bovis , ETBF, Roseburia spp. and E. faecalis in AP and CRC cases were achieved. Conclusion : Intestinal expression of TLR2, TLR4 and TLR5 is dynamic and depends on gut microbiota. Hence, altered immune activation in response to dysbiotic microbiota may promote intestinal inflammation in a group of patients with AP and CRC. Keyword: Adenomatous polyposis; colorectal cancer; gut microbiota; Toll-like receptors; intestinal inflammation

Improvement of immune response after radiofrequency ablation in colorectal cancer.

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. 102-102 ◽  
Author(s):  
Katia Lemdani ◽  
Nathalie Mignet ◽  
Johanne Seguin ◽  
Frederique Peschaud ◽  
Jean-François Emile ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Immune Response ◽  
Radiofrequency Ablation ◽  
T Lymphocytes ◽  
Immune Escape ◽  
Liver Tumors ◽  
Residual Disease ◽  
Checkpoint Inhibitors ◽  
T Cell Response

102 Background: Radiofrequency ablation (RFA) efficiency of liver tumors is compromised by high rates of relapse. Death of cancer cells by hyperthermia induced tumor antigen releasing, expression of danger signals that activate a specific T-cell response. This effect is ineffective to avoid recurrence. We propose to combine RFA with priming of a strong immune antitumor response as curative treatment of an aggressive colorectal cancer (CRC) in immunocompetent mouse. Methods: RFA was used to treat a CT26- luc tumor as primary lesion. In two distinct clinical situations, macroscopic or microscopic distant tumors were established as secondary lesions. The immune response was modulated by the injection, in the treated area, of a thermo-reversible hydrogel loaded by GM-CSF and BCG, targeting recruitment and maturation of dendritic cells. In mice with far large lesions, this strategy was combined with PD1checkpoint inhibition. The efficiency was assessed on survival, evolution of distant lesions, characterization of tumoral lymphocyte infiltration TNF-α and IFN-y expression in peripheral T lymphocytes. Results: The in situ immunogel injection after RFA resulted in prolonged survival of mice. Regression of distant lesions was related to the induction of a strong systemic antitumor immune response and a great improvement of tumor infiltration by CD3+ T lymphocytes. In adjuvant situation, the use of immunogel induced a complete cure of microscopic secondary lesions without another treatment. Immune escape of large secondary lesions was reversed by association of the RFA-immunogel vaccination with a systemic immune checkpoint inhibition, separately ineffective. Conclusions: Validation of this strategy, combining RFA of macroscopic lesions and activation of a strong immune response controlling the residual disease, could result in the design of a clinical assay including this approach within a standard treatment of colorectal liver metastases. The synergy between in situ immunomodulation as priming process and checkpoint blockade, ineffective alone in metastatic microsatellite stable CRC or after single RFA, allows reconsidering the use of checkpoint inhibitors in CRC.

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