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Published on: September 12, 2019
Sirolimus and liver transplantation: clinical implications for hepatocellular carcinoma
Jeffrey Campsen1, Michael A Zimmerman, James F Trotter
1University of Colorado Health Sciences Center, Division of Transplant Surgery, Denver, CO 80262, USA.
Abstract:
Sirolimus (SRL) is a macrolide antibiotic that has potent antifungal and immunosuppressive properties; preclinical studies suggest that SRL may possess a significant antiproliferative influence in vitro. Recently, several studies have documented a negative effect by SRL on both primary tumor growth and the proliferation of metastatic foci in various rodent models of hepatocellular carcinoma (HCC). Orthotopic liver transplantation (OLT) is increasingly becoming a viable treatment option for patients with end stage liver disease and concomitant HCC. As such, an immunosuppressive agent with antineoplastic activity is inherently attractive in the setting of OLT for malignancy. Regrettably, the cumulative experience with SRL-based immunosuppression in this patient population is limited. Herein, the authors review the experience to date with SRL as a primary immunosuppressive agent following OLT, and discuss the clinical implications of SRL-based therapy in OLT recipients with cirrhosis and cancer.
Insights
Sirolimus (SRL), an immunosuppressant, shows promise in slowing liver cancer growth. Its use after liver transplantation (OLT) for cancer is being explored due to potential anti-cancer effects.
Area of Science:
- Immunology
- Oncology
- Transplantation
Background:
- Sirolimus (SRL) is an antibiotic with immunosuppressive and antifungal properties.
- Preclinical data suggest SRL exhibits antiproliferative effects.
- Hepatocellular carcinoma (HCC) is a common complication of end-stage liver disease.
Purpose of the Study:
- To review the current experience with Sirolimus (SRL) as a primary immunosuppressant after liver transplantation (OLT).
- To discuss the clinical implications of SRL in OLT recipients with cancer.
Main Methods:
- Literature review of studies involving Sirolimus (SRL) in liver transplantation (OLT).
- Analysis of preclinical data on SRL's antiproliferative effects in hepatocellular carcinoma (HCC) models.
- Discussion of clinical outcomes and implications.
Main Results:
- Sirolimus (SRL) has demonstrated an inhibitory effect on primary tumor growth and metastasis in rodent models of hepatocellular carcinoma (HCC).
- Limited cumulative clinical experience exists for SRL-based immunosuppression in OLT recipients with cancer.
- SRL's antineoplastic properties make it an attractive option for OLT in cancer patients.
Conclusions:
- Sirolimus (SRL) presents a potential benefit in managing hepatocellular carcinoma (HCC) in liver transplant (OLT) recipients due to its antiproliferative activity.
- Further research and clinical data are needed to fully establish the role and safety of SRL in this patient population.
