Related Experiment Video
Updated: Jun 10, 2026
Development and Application of Rapamycin-regulated Tyrosine Phosphatases
Published on: September 6, 2024
Pilot study: rapamycin in advanced hepatocellular carcinoma
1Klinik Innere Medizin III, Abteilung für Gastroenterologie und Hepatologie, Medizinische Universität Wien, Vienna, Austria. maximilian.schoeniger-hekele@meduniwien.ac.at
Background:
The PI3K/Akt/mTOR signal pathway is involved in hepatocarcinogenesis. Rapamycin (=sirolimus), a specific mTOR inhibitor, leads to G(1) arrest of many malignant cell lines and currently, analogues of rapamycin are being investigated as a cancer chemotherapeutic adjuvant.
Aim:
To study the toxicity and tolerability of rapamycin therapy in patients with advanced hepatocellular carcinoma (HCC).
Methods:
Between June 2005 and February 2007, patients with advanced HCC, not eligible for any established therapy, were included in the study.
Results:
Eighteen patients (F/M: 5/13) with compensated liver cirrhosis (Child A n = 11, Child B n = 5, Child C n = 2) and histologically proven HCC were included in this study. According to the BCLC staging system, most of the patients enrolled had an advanced HCC: BCLC stage B: n = 2, Barcelona Clinic Liver-Cancer (BCLC) stage C: n = 14, BCLC stage D: n = 2. Overall, therapy with rapamycin was well tolerated. Most common toxicities were thrombocytopaenia and anaemia. We did not observe any partial or complete tumour response. At 3 months, two patients had stable disease and at 6 months, all patients had progressed. The median overall survival was 5.27 months, median time to progression was 3 months.
Conclusion:
Rapamycin is well tolerated in patients with advanced HCC, but only minimally effective.
Insights
Rapamycin therapy was well tolerated in patients with advanced hepatocellular carcinoma (HCC), but showed minimal effectiveness in tumor response and survival. Further research into mTOR inhibitors for HCC is warranted.
Area of Science:
- Oncology
- Pharmacology
- Hepatology
Background:
- The PI3K/Akt/mTOR pathway plays a role in liver cancer development.
- Rapamycin, an mTOR inhibitor, causes cell cycle arrest and is explored as a cancer treatment adjuvant.
Purpose of the Study:
- To evaluate the safety and tolerability of rapamycin in patients with advanced hepatocellular carcinoma (HCC).
Main Methods:
- A study included 18 patients with advanced HCC ineligible for standard therapies between June 2005 and February 2007.
- Patients had compensated liver cirrhosis (Child A/B/C) and confirmed HCC, with most at advanced BCLC stages C and D.
Main Results:
- Rapamycin treatment was generally well-tolerated, with the most frequent side effects being thrombocytopenia and anemia.
- No tumor responses were observed; median overall survival was 5.27 months, and median time to progression was 3 months.
Conclusions:
- Rapamycin demonstrates good tolerability in advanced HCC patients.
- However, rapamycin exhibits limited efficacy in treating advanced HCC.
