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Ref Type Journal Article
PMID (22896668)
Authors Hasenstein JR, Shin HC, Kasmerchak K, Buehler D, Kwon GS, Kozak KR
Title Antitumor activity of Triolimus: a novel multidrug-loaded micelle containing Paclitaxel, Rapamycin, and 17-AAG.
Journal Molecular cancer therapeutics
Vol 11
Issue 10
Date 2012 Oct
Abstract Text Triolimus is a first-in-class, multidrug-loaded micelle containing paclitaxel, rapamycin, and 17-AAG. In this study, we examine the antitumor mechanisms of action, efficacy, and toxicity of Triolimus in vitro and in vivo. In vitro cytotoxicity testing of Triolimus was conducted using two aggressive adenocarcinomas including the lung cancer cell line, A549, and breast cancer cell line, MDA-MB-231. The three-drug combination of paclitaxel, rapamycin, and 17-AAG displayed potent cytotoxic synergy in both A549 and MDA-MB-231 cell lines. Mechanistically, the drug combination inhibited both the Ras/Raf/mitogen-activated protein kinase and PI3K/Akt/mTOR pathways. Triolimus was advanced into tumor xenograft models for assessment of efficacy, toxicity, and mechanisms of action. In vivo, a three-infusion schedule of Triolimus inhibited A549 and MDA-MB-231 tumor growth far more potently than paclitaxel-containing micelles and effected tumor cures in MDA-MB-231 tumor-bearing animals. Tumor growth delays resulted from a doubling in tumor cell apoptosis and a 50% reduction in tumor cell proliferation compared with paclitaxel-containing micelles. Enhanced antitumor efficacy was achieved without clinically significant increases in acute toxicity. Thus, Triolimus displays potent synergistic activity in vitro and antitumor activity in vivo with comparable toxicity to paclitaxel. These observations provide strong support for further development of Triolimus and an important proof of concept for safe, effective nanoparticle-based delivery of three complementary anticancer agents.


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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Triolimus Triolimus 2 0
Drug Name Trade Name Synonyms Drug Classes Drug Description
Triolimus Antimicrotubule Agent 12 HSP90 Inhibitor 35 mTORC1 Inhibitor 8 Triolimus is a composed of a micelle containing the drugs rapamycin, 17-AAG, and paclitaxel, which act synergistically to inhibit tumor growth (PMID: 22896668, PMID: 27365266).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
Unknown unknown breast cancer not applicable Triolimus Preclinical - Cell line xenograft Actionable In a preclinical study, Triolimus led to cytotoxicity and inhbition of Ras/Raf/MAPK and PI3K/Akt/mTOR pathway signaling in breast cancer cells in culture and inhibited tumor growth in cell line xenograft models (PMID: 22896668). 22896668
Unknown unknown lung cancer not applicable Triolimus Preclinical - Cell line xenograft Actionable In a preclinical study, Triolimus led to cytotoxicity and inhibited Ras/Raf/MAPK and PI3K/Akt/mTOR pathway signaling in lung cancer cells in culture, and induced apoptosis, which resulted in tumor growth inhibition, in cell line xenograft models (PMID: 22896668). 22896668