Role of the microbiome in systemic therapy for pancreatic ductal adenocarcinoma (Review)

Huang, Xing; Li, Mao; Hou, Shengzhong; Tian, Bole

doi:10.3892/ijo.2021.5281

Cited by 7 publications

(4 citation statements)

References 135 publications

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“…show that a large proportion of human PDAC samples are positive for Gammaproteobacteria which express cytidine deaminase. Cytidine deaminase directly contributes to treatment resistance by degrading gemcitabine into its inactive form ( 103 , 104 ). While co-administration with ciprofloxacin seems to abrogate these effects ( 103 ), organizations such as the FDA are critical about antibiotic stewardship ( 20 ).…”

Section: Perspective On Bacterial Immunotherapy Of Pdacmentioning

confidence: 99%

Emerging applications of cancer bacteriotherapy towards treatment of pancreatic cancer

Henderson,

Lukomski,

Boone

2023

Front. Oncol.

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Pancreatic cancer is a highly aggressive form of cancer with a five-year survival rate of only ten percent. Pancreatic ductal adenocarcinoma (PDAC) accounts for ninety percent of those cases. PDAC is associated with a dense stroma that confers resistance to current treatment modalities. Increasing resistance to cancer treatments poses a challenge and a need for alternative therapies. Bacterial mediated cancer therapies were proposed in the late 1800s by Dr. William Coley when he injected osteosarcoma patients with live streptococci or a fabrication of heat-killed Streptococcus pyogenes and Serratia marcescens known as Coley’s toxin. Since then, several bacteria have gained recognition for possible roles in potentiating treatment response, enhancing anti-tumor immunity, and alleviating adverse effects to standard treatment options. This review highlights key bacterial mechanisms and structures that promote anti-tumor immunity, challenges and risks associated with bacterial mediated cancer therapies, and applications and opportunities for use in PDAC management.

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Section: Perspective On Bacterial Immunotherapy Of Pdacmentioning

confidence: 99%

Emerging applications of cancer bacteriotherapy towards treatment of pancreatic cancer

Henderson,

Lukomski,

Boone

2023

Front. Oncol.

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“…There are many reasons that may explain the low response rates of PDAC to systemic chemotherapy. Recently, the influence of the microbiome has become of interest [82,83] and may even provide insight or future direction to improve the responsiveness of PDAC to immunotherapy. As previously noted, a compositional difference in the intratumoral microbiota has been shown in long-term vs short-term survivors of PDAC after surgery and adjuvant systemic chemotherapy [12].…”

Section: The Relationship Of the Microbiome With Conventional Chemoth...mentioning

confidence: 99%

The Prospect of Harnessing the Microbiome to Improve Immunotherapeutic Response in Pancreatic Cancer

Rogers,

Charles,

Thomas

2023

Cancers

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Pancreatic ductal adenocarcinoma cancer (PDAC) is projected to become the second leading cause of cancer-related death in the United States by 2030. Patients are often diagnosed with advanced disease, which explains the dismal 5-year median overall survival rate of ~12%. Immunotherapy has been successful in improving outcomes in the past decade for a variety of malignancies, including gastrointestinal cancers. However, PDAC is historically an immunologically “cold” tumor, one with an immunosuppressive environment and with restricted entry of immune cells that have limited the success of immunotherapy in these tumors. The microbiome, the intricate community of microorganisms present on and within humans, has been shown to contribute to many cancers, including PDAC. Recently, its role in tumor immunology and response to immunotherapy has generated much interest. Herein, the current state of the interaction of the microbiome and immunotherapy in PDAC is discussed with a focus on needed areas of study in order to harness the immune system to combat pancreatic cancer.

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“…Nevertheless, many patients develop resistance or toxicity to these drugs [202]. Consequently, these adverse events may necessitate drug dose reduction to make the treatment tolerable or suspension before the treatment completion date [203]. It is worth noting that the resulting microbial dysbiosis from PC can promote its pathogenesis and affect therapeutic outcomes.…”

Section: Microbiota and Microbial Metabolites In Pc Therapymentioning

confidence: 99%

“…One of the agents used in FOLFIRINOX treatment is irinotecan (CPT-11), which occasionally results in toxicity, thus limiting the efficacy and regimen use. In addition, one of the typical clinical effects of irinotecan is delayed onset diarrhoea, thus suggesting that this drug can alter the gut microbiota profile [203]. Lin et al demonstrated that irinotecan-based treatment altered intestinal microbiota in tumour-bearing rat models [226].…”

Section: Chemo/radiotherapymentioning

confidence: 99%

Bile Acids and Microbiota Interplay in Pancreatic Cancer

Malhotra

Palanisamy

Caparrós-Martín

et al. 2023

Cancers

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Evidence suggests the involvement of the microbiota, including oral, intra-tumoral and gut, in pancreatic cancer progression and response to therapy. The gut microbiota modulates the bile acid pool and is associated with maintaining host physiology. Studies have shown that the bile acid/gut microbiota axis is dysregulated in pancreatic cancer. Bile acid receptor expression and bile acid levels are dysregulated in pancreatic cancer as well. Studies have also shown that bile acids can cause pancreatic cell injury and facilitate cancer cell proliferation. The microbiota and its metabolites, including bile acids, are also altered in other conditions considered risk factors for pancreatic cancer development and can alter responses to chemotherapeutic treatments, thus affecting patient outcomes. Altogether, these findings suggest that the gut microbial and/or bile acid profiles could also serve as biomarkers for pancreatic cancer detection. This review will discuss the current knowledge on the interaction between gut microbiota interaction and bile acid metabolism in pancreatic cancer.

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Role of the microbiome in systemic therapy for pancreatic ductal adenocarcinoma (Review)

Cited by 7 publications

References 135 publications

Emerging applications of cancer bacteriotherapy towards treatment of pancreatic cancer

Emerging applications of cancer bacteriotherapy towards treatment of pancreatic cancer

The Prospect of Harnessing the Microbiome to Improve Immunotherapeutic Response in Pancreatic Cancer

Bile Acids and Microbiota Interplay in Pancreatic Cancer

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