Tumour growth in the regenerating liver
AuthorRiddiough, Georgina Ellen
AffiliationSurgery (Austin & Northern Health)
Document TypePhD thesis
Access StatusThis item is embargoed and will be available on 2023-10-13. This item is currently available to University of Melbourne staff and students only, login required.
© 2021 Georgina Ellen Riddiough
Post-partial hepatectomy liver regeneration (PHLR) facilitates major hepatic resection by reinstating liver volume and function. However, experimental and clinical data has linked PHLR to tumour progression and recurrence in the future liver remnant following liver resection. This presents a major hurdle for hepatobiliary surgeons seeking curative resections for their patients. This thesis explores the mechanisms underlying tumour recurrence in the regenerating liver and investigates the role of renin-angiotensin inhibitors (RASi) in attenuating the growth of colorectal liver metastasis (CRLM) using murine and human models of CRLM disease. RASi, captopril attenuated CRLM tumour burden in the regenerating liver in vivo and underlying mechanisms for this were identified and included reprogramming of the immune and metabolic responses, as well as tumour specific downregulation of the proto-oncogene c-myc. Captopril also attenuated growth of patient-derived CRLM organoids in vitro. In summary, captopril exerts an effective anti-tumour response in the regenerating liver and should be pursued as a treatment adjunct for patients undergoing liver resection for CRLM.
Keywordscolorectal liver metastasis; liver regeneration; immunology; surgical oncology; liver neoplasms
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