key papersKey paper
Clinical activity of mTOR inhibition with sirolimus in malignant perivascular epithelioid cell tumours
This report of three patients with malignant PEComa responding to oral sirolimus was the first evidence that these tumours, which share TSC1/TSC2 loss with tuberous sclerosis, depend on the mTOR pathway.
Overview
Case series of three patients with metastatic malignant PEComa treated with sirolimus, all showing radiological responses, with molecular analysis of tumour tissue demonstrating loss of TSC2 and activation of mTORC1 signalling.
Observational studyChanged practice3 participants
Authors
Wagner AJ, Malinowska-Kolodziej I, Morgan JA, et al.
Published
Findings
- Radiological responses in all three patients treated with sirolimus.
- TSC2 loss and mTORC1 activation in tumour tissue.
What it means
mTOR inhibition became the therapeutic strategy for PEComa, culminating in the AMPECT trial and approval of nab-sirolimus.
Caveats
- Three patients; hypothesis-generating.