A Pilot Study of Sirolimus in Subjects with Cowden Syndrome or Other Syndromes Characterized by Germline Mutations in PTEN.

ABSTRACT:

Lessons learned

This is the first human interventional study in patients with Cowden syndrome that is driven by inactivation of germline PTEN gene.Single-agent sirolimus, a mTOR inhibitor, suppressed mTOR signaling in surrogate human tissues without significant toxicity.

Background

Cowden syndrome is characterized by inactivating germline PTEN mutations, which can lead to activation of the PI3K-Akt-mTOR pathway.

Methods

Adult subjects with germline PTEN mutation who met international diagnostic criteria for Cowden syndrome and who had Eastern Cooperative Oncology Group (ECOG) performance status 0-2 and adequate organ function were enrolled. Subjects were treated with a 56-day course of daily oral sirolimus. In addition to symptom assessment and ph

SUBMITTER: Komiya T 

PROVIDER: S-EPMC6975943 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature