The Emerging Role of Microbiota and Microbiome in Pancreatic Ductal Adenocarcinoma

Ciernikova, Sona; Novisedlakova, Maria; Cholujová, Dana; Stevurkova, Viola; Mego, Michal

doi:10.3390/biomedicines8120565

Cited by 16 publications

(22 citation statements)

References 118 publications

(132 reference statements)

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“…A study reviewed clinical trials of the role of the microbiota in the risk, prognosis, and treatment of patients with pancreatic ductal adenocarcinoma (PDAC) and solid tumors. According to the results, microbiome analysis represents a potential trend to enhance antitumor immunity and improve the efficacy of PDAC treatment [ 74 ]. Chaput et al conducted a follow-up study on patients with metastatic melanoma treated with ipilimumab (a CTLA-4 inhibitor) and found that patients with a predominant phylum Firmicutes in the gut microbiota have a better treatment effect.…”

Section: Application Of Gut Microbiota In Tumor Immunotherapymentioning

confidence: 99%

The Role of Gut Microbiota in Tumor Immunotherapy

Bai

et al. 2021

Journal of Immunology Research

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Tumor immunotherapy is the fourth therapy after surgery, chemotherapy, and radiotherapy. It has made great breakthroughs in the treatment of some epithelial tumors and hematological tumors. However, its adverse reactions are common or even more serious, and the response rate in some solid tumors is not satisfactory. With the maturity of genomics and metabolomics technologies, the effect of intestinal microbiota in tumor development and treatment has gradually been recognized. The microbiota may affect tumor immunity by regulating the host immune system and tumor microenvironment. Some bacteria help fight tumors by activating immunity, while some bacteria mediate immunosuppression to help cancer cells escape from the immune system. More and more studies have revealed that the effects and complications of tumor immunotherapy are related to the composition of the gut microbiota. The composition of the intestinal microbiota that is sensitive to treatment or prone to adverse reactions has certain characteristics. These characteristics may be used as biomarkers to predict the prognosis of immunotherapy and may also be developed as “immune potentiators” to assist immunotherapy. Some clinical and preclinical studies have proved that microbial intervention, including microbial transplantation, can improve the sensitivity of immunotherapy or reduce adverse reactions to a certain extent. With the development of gene editing technology and nanotechnology, the design and development of engineered bacteria that contribute to immunotherapy has become a new research hotspot. Based on the relationship between the intestinal microbiota and immunotherapy, the correct mining of microbial information and the development of reasonable and feasible microbial intervention methods are expected to optimize tumor immunotherapy to a large extent and bring new breakthroughs in tumor treatment.

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Section: Application Of Gut Microbiota In Tumor Immunotherapymentioning

confidence: 99%

The Role of Gut Microbiota in Tumor Immunotherapy

Bai

et al. 2021

Journal of Immunology Research

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“…Fortunately, there are already ongoing randomized clinical trials that combine 16S rRNA gene analysis, FMT or probiotics along with chemotherapeutics and are listed in the review by Ciernikova et al. ( 57 ). The upcoming results may thus further substantiate the interrelationship of the host`s microbiome and tumor cells and provide the basis of novel therapeutic concepts of PDAC therapy.…”

Section: The Microbiome - Pdac Axismentioning

confidence: 99%

The Microbiome Tumor Axis: How the Microbiome Could Contribute to Clonal Heterogeneity and Disease Outcome in Pancreatic Cancer

et al. 2021

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Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant cancers. It is characterized by a poor prognosis with a 5-year survival rate of only around 10% and an ongoing increase in death rate. Due to the lack of early and specific symptoms, most patients are diagnosed at an advanced or even metastasized stage, essentially limiting curative treatment options. However, even curative resection of the primary tumor and adjuvant therapy often fails to provide a long-term survival benefit. One reason for this dismal situation can be seen in the evolution of therapy resistances. Furthermore, PDAC is characterized by high intratumor heterogeneity, pointing towards an abundance of cancer stem cells (CSCs), which are regarded as essential for tumor initiation and drug resistance. Additionally, it was shown that the gut microbiome is altered in PDAC patients, promotes Epithelial-Mesenchymal-Transition (EMT), determines responses towards chemotherapy, and affects survival in PDAC patients. Given the established links between CSCs and EMT as well as drug resistance, and the emerging role of the microbiome in PDAC, we postulate that the composition of the microbiome of PDAC patients is a critical determinant for the abundance and plasticity of CSC populations and thus tumor heterogeneity in PDAC. Unravelling this complex interplay might pave the way for novel treatment strategies.

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“…Interestingly, emerging evidence suggests a novel mechanism for the positive effect of metformin in PDAC patients. Several studies have demonstrated that microbiome plays a role in oncogenesis and can modulate cancer treatment response in several cancer types, including PDAC [ 103 , 104 , 105 , 106 , 107 , 108 , 109 ]. Moreover, several studies have reported that metformin modulates the gut microbiota in T2DM models, suggesting that its antidiabetic effect is also microbial-dependent [ 110 , 111 , 112 ].…”

Section: Drug Repurposing Candidates For Pancreatic Cancer Treatmementioning

confidence: 99%

Drug Repurposing Opportunities in Pancreatic Ductal Adenocarcinoma

et al. 2021

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Pancreatic ductal adenocarcinoma (PDAC) is considered one of the deadliest tumors worldwide. The diagnosis is often possible only in the latter stages of the disease, with patients already presenting an advanced or metastatic tumor. It is also one of the cancers with poorest prognosis, presenting a five-year survival rate of around 5%. Treatment of PDAC is still a major challenge, with cytotoxic chemotherapy remaining the basis of systemic therapy. However, no major advances have been made recently, and therapeutic options are limited and highly toxic. Thus, novel therapeutic options are urgently needed. Drug repurposing is a strategy for the development of novel treatments using approved or investigational drugs outside the scope of the original clinical indication. Since repurposed drugs have already completed several stages of the drug development process, a broad range of data is already available. Thus, when compared with de novo drug development, drug repurposing is time-efficient, inexpensive and has less risk of failure in future clinical trials. Several repurposing candidates have been investigated in the past years for the treatment of PDAC, as single agents or in combination with conventional chemotherapy. This review gives an overview of the main drugs that have been investigated as repurposing candidates, for the potential treatment of PDAC, in preclinical studies and clinical trials.

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The Emerging Role of Microbiota and Microbiome in Pancreatic Ductal Adenocarcinoma

Cited by 16 publications

References 118 publications

The Role of Gut Microbiota in Tumor Immunotherapy

The Role of Gut Microbiota in Tumor Immunotherapy

The Microbiome Tumor Axis: How the Microbiome Could Contribute to Clonal Heterogeneity and Disease Outcome in Pancreatic Cancer

Drug Repurposing Opportunities in Pancreatic Ductal Adenocarcinoma

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