Please use this identifier to cite or link to this item: http://buratest.brunel.ac.uk/handle/2438/13642
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dc.contributor.authorHarvey, A-
dc.contributor.authorHare, SH-
dc.date.accessioned2016-12-14T15:07:44Z-
dc.date.available2016-12-14T15:07:44Z-
dc.date.issued2017-
dc.identifier.citationAmerican Journal of Cancer Research, (2017)en_US
dc.identifier.issn2156-6976-
dc.identifier.urihttp://bura.brunel.ac.uk/handle/2438/13642-
dc.description.abstractThe mTOR pathway was discovered in the late 1970s after the compound and natural inhibitor of mTOR, rapamycin was isolated from the bacterium Streptomyces hygroscopicus. mTOR is serine/threonine kinase belonging to the phosphoinositide 3-kinase related kinase (PIKK) family. It forms two distinct complexes; mTORC1 and mTORC2. mTORC1 has a key role in regulating protein synthesis and autophagy whilst mTORC2 is involved in regulating kinases of the AGC family. mTOR signaling is often over active in multiple cancer types including breast cancer. This can involve mutations in mTOR itself but more commonly, in breast cancer, this is related to an increase in activity of ErbB family receptors or alterations and mutations of PI3K signaling. Rapamycin and its analogues (rapalogues) bind to the intercellular receptor FKBP12, and then predominantly inhibit mTORC1 signaling via an allosteric mechanism. Research has shown that inhibition of mTOR is a useful strategy in tackling cancers, with it acting to slow tumor growth and limit the spread of a cancer. Rapalogues have now made their way into the clinic with the rapalogue everolimus (RAD-001/Afinitor) approved for use in conjunction with exemestane, in post-menopausal breast cancer patients with advanced disease who are HER-2 negative (normal expression), hormone receptor positive and whose prior treatment with non-steroidal aromatase inhibitors has failed. Testing across multiple trials has proven that everolimus and other rapalogues are a viable way of treating certain types of cancer. However, rapalogues have shown some drawbacks both in research and clinically, with their use often activating feedback pathways that counter their usefulness. As such, new types of inhibitors are being explored that work via different mechanisms, including inhibitors that are ATP competitive with mTOR and which act to perturb signaling from both mTOR complexes.en_US
dc.language.isoenen_US
dc.publishere-Century Publishingen_US
dc.subjectmTORen_US
dc.subjectRapaloguesen_US
dc.subjectBreast canceren_US
dc.subjectCell signalingen_US
dc.subjectEverolimusen_US
dc.subjectPI3Ken_US
dc.titleMTOR function and therapeutic targeting in breast canceren_US
dc.typeArticleen_US
dc.relation.isPartOfAmerican Journal of Cancer Research-
pubs.publication-statusAccepted-
Appears in Collections:Dept of Life Sciences Research Papers

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