Targeting Autophagy Addiction in Cancer

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Targeting Autophagy Addiction in Cancer

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dc.contributor.author Mancias, Joseph Douglas
dc.contributor.author Kimmelman, Alec C.
dc.date.accessioned 2012-04-08T19:01:01Z
dc.date.issued 2011
dc.identifier.citation Mancias, Joseph D., and Alec C. Kimmelman. 2011. Targeting Autophagy Addiction in Cancer. Oncotarget 12(2): 1302-1306. en_US
dc.identifier.issn 1949-2553 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:8519638
dc.description.abstract Autophagy inhibition is a novel cancer therapeutic strategy in the early stages of clinical trial testing. The initial rationale for using autophagy inhibition was generated by research revealing that autophagy is upregulated in response to external stresses, including chemotherapy and radiotherapy. Combining autophagy inhibition with agents that induce autophagy as a pro-survival response may therefore increase their therapeutic efficacy. Recent research has shown that some cancer cells, particularly those driven by the K-Ras oncogene, also depend on elevated levels of autophagy for survival even in the absence of external stressors. In multiple in vitro as well as in vivo systems, oncogenic Ras-mediated transformation and tumor growth are dependent on autophagy to evade metabolic stress and cell death. These studies have subsequently led to further early phase clinical testing whether autophagy inhibition is a viable and effective strategy for targeting Ras-driven tumors. Even before the clinical results are available from these ongoing clinical trials, much work remains to optimally develop the approach of autophagy inhibition clinically; most notably reliably detecting levels of autophagy in human tumor samples, pharmacodynamics of currently available autophagy inhibitors (chloroquine and the derivative hydroxychloroquine), and new target identification and drug development. en_US
dc.language.iso en_US en_US
dc.publisher Impact Journals LLC en_US
dc.relation.isversionof http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=384 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3282086/pdf/ en_US
dash.license LAA
dc.subject autophagy en_US
dc.subject Ras en_US
dc.subject metabolism en_US
dc.subject cancer en_US
dc.subject tumor en_US
dc.subject therapy en_US
dc.title Targeting Autophagy Addiction in Cancer en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal Oncotarget en_US
dash.depositing.author Kimmelman, Alec C.
dc.date.available 2012-04-08T19:01:01Z

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