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Updated: Dec 18, 2025
Isolated Hepatic Perfusion as a Treatment for Liver Metastases of Uveal Melanoma
Published on: January 25, 2015
Medical treatment of advanced malignant perivascular epithelioid cell tumors
Chiara Fabbroni1, Marta Sbaraglia2, Roberta Sanfilippo1
1Medical Oncology Unit 2, Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan.
Purpose Of Review:
Malignant PEComa are rare mesenchymal tumors characterized by genetic alterations actionable by target therapy. Indeed, they harbour loss of function of TSC1/TSC2, which lead to the activation of the mammalian target of rapamycin (mTOR) pathway, which is targetable therapeutically with mTOR inhibitors like sirolimus. A small subset of malignant PEComas instead harbor TFE3 gene fusions known to be mutually exclusive with TSC1/TSC2 loss-of-function mutations; therefore, leading to different therapeutic implication.
Recent Findings:
mTOR inhibitors showed a response rate around 40% with a median PFS of 9 months both in retrospective case series than in phase 2 prospective clinical trials, therefore, representing the most active therapeutic drug. Up to now, the issue is the lack of further therapeutic lines in the advanced setting. Chemotherapy has a marginal role, while some responses were reported using Vascular endothelial growth factor-Tyrosine kynase inhibitors (VEGF-TKI) inhibitors.
Summary:
Malignant PEComas display some sensitivity to mTOR inhibitors. If progression thereto, no other drugs are available. Preclinical studies are ongoing to explore the potential combination of hormonal blockade in women and the potential use of PD1 checkpoint inhibitors.
Insights
Malignant PEComas, rare tumors, respond to mTOR inhibitors, offering a 40% response rate. However, limited options exist for advanced disease, necessitating research into new therapies like VEGF-TKIs and immunotherapy.
Area of Science:
- Oncology
- Genetics
- Pharmacology
Background:
- Malignant PEComas are rare mesenchymal tumors with actionable genetic alterations.
- Key genetic drivers include TSC1/TSC2 loss-of-function mutations activating the mTOR pathway, or TFE3 gene fusions.
- These genetic profiles have distinct therapeutic implications.
Purpose of the Study:
- To review the therapeutic landscape for malignant PEComas.
- To highlight the efficacy and limitations of current treatments, particularly mTOR inhibitors.
- To identify unmet needs and future therapeutic directions.
Main Methods:
- Review of retrospective case series and prospective clinical trials.
- Analysis of treatment response rates and progression-free survival (PFS) for mTOR inhibitors.
- Evaluation of alternative therapies including chemotherapy and VEGF-TKIs.
Main Results:
- mTOR inhibitors demonstrate a response rate of approximately 40% with a median PFS of 9 months.
- Chemotherapy has a limited role in managing advanced malignant PEComas.
- Some responses have been observed with Vascular Endothelial Growth Factor-Tyrosine Kinase Inhibitors (VEGF-TKIs).
Conclusions:
- Malignant PEComas show sensitivity to mTOR inhibitors, which are the most active therapeutic agents currently available.
- There is a significant unmet need for effective therapies in the advanced setting after progression on mTOR inhibitors.
- Ongoing preclinical research is exploring combinations with hormonal blockade and PD1 checkpoint inhibitors.
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