Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster Display session

204P - Dysbiosis of the gut microbiome impairs EGFR-tyrosine kinase inhibitors responses in H1975 xenografts mice models

Date

31 Mar 2023

Session

Poster Display session

Presenters

Yu-MU Chen

Citation

Journal of Thoracic Oncology (2023) 18 (4S): S149-S153.
<article-id>elcc_Ch10

Authors

Y. Chen1, W. Lian2, F. Wang2, C. Hsiao3, M. Lin4

Author affiliations

  • 1 Kaohsiung City/TW
  • 2 Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung City/TW
  • 3 Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Taoyuan/TW
  • 4 Chang Gung Medical Foundation - Kaohsiung Chang Gung Memorial Hospital, Kaohsiung City/TW

Resources

Login to access the resources on OncologyPRO.

If you do not have an ESMO account, please create one for free.

Abstract 204P

Background

Proton Pump Inhibitor-Induced Gut Dysbiosis has been demonstrated in previous studies and was associated with poor prognosis in patients received immunotherapies and chemotherapies. However, little is known about the influence of Proton Pump Inhibitor-Induced dysbiosis on efficacies of target therapies like epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs). We conduct a study to elucidate the role of PPI related dysbiosis on EGFR-TKIs efficacies.

Methods

Female BALB/c Mice were raised in specific pathogen-free (SPF) conditions and treated for 14 days proton pump inhibitor, lansoprazole (5 mg/kg) or control. Microbial was tested using NGS with the computational analysis of targeted (16S rRNA hypervariable regions). BALB/c mice were implanted with 5 × 106 H1975 NSCLC subcutaneously and treated orally when tumors reached 20 to 35 mm2 in size with EGFR-TKIs, Osimertinib (1 mg/kg/day). Feces were cultured on 5% sheep blood enriched Columbia Agar for aerobic and anaerobic conditions, respectively.

Results

Our study revealed PPI impaired TKI effectiveness in H1975 xenografts mice models (tumor fold change, with vs. without PPI: 28.1 vs. 7.4, p = 0.043). The feces culturomic analyses revealed Clostridiales vadin BB60 group was more abundances in xenogeneic EGFR-TKIs mice treated with PPI than without. The optimal cut-off point of relative abondance of operational taxonomic units (OTU) for Clostridiales vadin BB60 group determined by the ROC curve was 10.9%, p = 0.046. Mice with high abundance of Clostridiales vadin BB60 group had higher D17 tumor volume fold change (high vs low abundance of Clostridiales vadin BB60 group: 34.0 vs. 8.1, p = 0.025). Another taxa lactobacillus was more abundances in xenogeneic EGFR-TKIs treated mice with PPI than without. The optimal cut-off point of relative abondance of operational taxonomic units (OTU) for lactobacillus determined by the ROC was 0.3%, p < 0.001. Mice with high abundance of lactobacillus had higher D17 tumor volume fold change than mice with low abundance (tumor fold change 43.6 vs. 9.1, p = 0.04) by Mann-Whitney test.

Conclusions

Our study revealed PPI related dysbiosis are associated with poor EGFR-TKIs response in H1975 xenografts Mice.

Clinical trial identification

The Institutional Animal Care and Use Committee approved animal operative and experimental processes in Kaohsiung Chang Gung Memorial Hospital (Affidavit No. 2020030503).

Legal entity responsible for the study

The authors.

Funding

Kaohsiung Chang Gung Memorial Hospital.

Disclosure

All authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.