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from a new review article on mTor inhibitors
COMBINATION OF mTOR-TARGETED THERAPIES AND OTHER
ANTICANCER AGENTS
Combination With Trastuzumab
In HER-2–positive breast cancer cell lines, trastuzumab has been
shown to inhibit feedback-loop activation of Akt.94 This is especially
notable as PTEN loss is a known mediator of trastuzumab resis-
tance,95,96 providing another rationale to use mTOR inhibitors to
restore or enhance trastuzumab sensitivity. In vitro, low doses of
everolimus significantly increased growth inhibition by trastuzumab,
and in vivo everolimus enhanced the antitumor efficacy of trastu-
zumab by a modest amount.94 The combination of everolimus and
trastuzumab is currently in clinical trials. A recent multicenter phase I
trial of everolimus in combination with paclitaxel and trastuzumab in
patients with HER-2– overexpressing metastatic breast cancer with
prior resistance to trastuzumab demonstrated that the combination
was well tolerated, with the preliminary evidence of efficacy.97
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