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Recent Clinical Trials of mTOR-Targeted Cancer Therapies

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The mammalian target of rapamycin (mTOR) is a central component within a complex intracellular signaling network that regulates various processes including cell growth, proliferation, metabolism, and angiogenesis. A hyperactive PI3k/Akt/mTOR signaling pathway is found in many human cancers and alterations in this pathway are associated with the development and progression of cancer. Drugs that target and inhibit mTOR activity are therefore expected to provide therapeutic value in a number of cancer types. Several classes of mTOR-targeted therapeutics are currently being evaluated in cancer clinical trials, including the rapamycins, dual PI3K-mTOR inhibitors, and ATP-competitive mTORC1/2 inhibitors. This review summarizes important findings from recently completed trials of mTOR inhibitors and also discusses preliminary data from ongoing trials.

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Keywords: ATP-competitive mTORC1/2 inhibitors; Abraxane; Advanced gastric cancer; Advanced low-tointermediate grade neuroendocrine tumors (LGNETs); Advanced solid tumors (ovarian, uterine, colorectal, pancreatic, and head and neck cancers); Akt/PKB (protein kinase B); Cancer clinical trials; DNA damage; Dual PI3K-mTOR inhibitors; Everolimus; Everolimus Octreotide (somatostatin analog) LAR (long-acting repeatable); Everolimus trastuzumab (anti-HER2 agent) paclitaxel; FKBP12; FKBP12-rapamycin binding; FRB; HER2-positive metastatic breast cancer; MCL; NEC; Nab-rapamycin; PIP2; PIP3; PTEN; Phosphatase and tensin homolog deleted on chromosome ten; RCC; Rapamycin (Sirolimus); Rapamycins; Raptor; Recurrent malignant glioma; Ridaforolimus; Ridaforolimus bevacizumab (anti-VEGF agent); Ridaforolimus trastuzumab (anti-HER2 agent); S6K1 gene; Sirolimus gefitinib (anti-EGFR agent); Streptomyces hygroscopicus; TSC (tuberous sclerosis protein complex); TSC1 (hamartin)/TSC2 (tuberin); albumin-bound nabTM-paclitaxel; amino acids, glucose; angiogenesis; colorectal cancer; hepatocellular cancer (HCC); heterodimer; insulin, IGF1; mLst8/GL; mSin1; mSin2; mTOR; mTOR-targeted therapeutics; msin3/Rictor; neuroendocrine cancer (NEC); oxidative; pancreas (adenocarcinoma); phosphatidylinositol 3-kinase (PI 3-kinase)-related kinase (PIKK); protor; ribosome biogenesis; sarcoma; serine/threonine kinase; sirolimus

Document Type: Research Article

Publication date: January 1, 2011

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  • Reviews on Recent Clinical Trials publishes frontier reviews on recent clinical trials of major importance. The journal's aim is to publish the highest quality review articles in the field. Topics covered include: important Phase I - IV clinical trial studies, clinical investigations at all stages of development and therapeutics.

    The journal is essential reading for all researchers and clinicians involved in drug therapy and clinical trials.
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