Therapeutic potential of mTOR inhibitors for targeting cancer stem cells.

@article{Francipane2016TherapeuticPO,
  title={Therapeutic potential of mTOR inhibitors for targeting cancer stem cells.},
  author={Maria Giovanna Francipane and Eric Lagasse},
  journal={British journal of clinical pharmacology},
  year={2016},
  volume={82 5},
  pages={
          1180-1188
        },
  url={https://api.semanticscholar.org/CorpusID:3578225}
}
Results provide a compelling rationale for the clinical development of mTOR-targeted therapies and show a preferential inhibitory effect on CSCs has already been shown for some mTOR inhibitors.
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78 References

PtdIns(3,4,5)P3-Dependent Activation of the mTORC2 Kinase Complex.

This study unravels a PI3K-dependent mechanism for mTORC2 activation, allowing m TORC2 to activate AKT in a manner that is regulated temporally and spatially by PtdIns(3,4,5)P3.

mTOR inhibitors counteract tamoxifen-induced activation of breast cancer stem cells.

Clinical efficacy of mTOR inhibitors in solid tumors: a systematic review.

Analysis of published clinical trials on solid tumors other than renal cell cancer, neuroendocrine tumors and metastatic breast cancer found a lack of therapeutic effects was observed when mTOR inhibitors were used as a single agent and when combined with other agents.

mTOR Inhibition Induces EGFR Feedback Activation in Association with Its Resistance to Human Pancreatic Cancer

The in vitro and in vivo experiments indicated the combination of AZD8055 and erlotinib synergistically inhibited the mTORC1/C2 signaling pathway, EGFR/AKT feedback activation, and cell growth, as well as suppressed the progression of pancreatic cancer in a xenograft model.

PI3K/mTOR dual inhibitor VS-5584 preferentially targets cancer stem cells.

It is reported that VS-5584 is up to 30-fold more potent in inhibiting the proliferation and survival of CSC compared with non-CSC in solid tumor cell populations, and suggested that combining VS- 5584 with classic chemotherapy that debulks tumors may engender a more effective strategy to achieve durable remissions in patients with cancer.

Suppression of Feedback Loops Mediated by PI3K/mTOR Induces Multiple Overactivation of Compensatory Pathways: An Unintended Consequence Leading to Drug Resistance

The development of drug resistance by cancer cells is recognized as a major cause for drug failure and disease progression. The PI3K/AKT/mTOR pathway is aberrantly stimulated in many cancer cells and…

Apoptosis Therapy in Cancer: The First Single-molecule Co-activating p53 and the Translocator Protein in Glioblastoma

It is suggested that TSPO/MDM2 dual-target ligands could represent a new attractive multi-modal opportunity for anti-cancer strategy in GBM.

Evolution of the cancer stem cell model.

A diverse array of cancer-associated MTOR mutations are hyperactivating and can predict rapamycin sensitivity.

Using publicly available tumor genome sequencing data, a comprehensive catalog of mTOR pathway mutations in cancer is generated, identifying 33 MTOR mutations that confer pathway hyperactivation and displaying heightened sensitivity to rapamycin both in culture and in vivo xenografts, suggesting that such mutations confer m TOR pathway dependency.

Navigating the challenge of tumor heterogeneity in cancer therapy.

A path for functional validation of computational modeling in the context of heterogeneous tumor populations and their potential for drug response and resistance is defined.
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