human
The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
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    INPUT: The phosphoinositide 3-kinase ( PI3K)/AKT and RAF/MEK/ERK signaling pathways are activated in a wide range of human cancers . In many cases , concomitant inhibition of both pathways is necessary to block proliferation and induce cell death and tumor shrinkage . Several feedback systems have been described in which inhibition of one intracellular pathway leads to activation of a parallel signaling pathway , thereby decreasing the effectiveness of single-agent targeted therapies . In this study , we describe a feedback mechanism in which MEK inhibition leads to activation of PI3K/AKT signaling in EGFR and HER2-driven cancers . We found that MEK inhibitor-induced activation of PI3K/AKT resulted from hyperactivation of ERBB3 as a result of the loss of an inhibitory threonine phosphorylation in the conserved juxtamembrane domains of EGFR and HER2 . Mutation of this amino acid led to increased ERBB receptor activation and upregulation of the ERBB3/PI3K/AKT signaling pathway , which was no longer responsive to MEK inhibition . Taken together , these results elucidate an important , dominant feedback network regulating central oncogenic pathways in human cancer .
    OUTPUT:

agent
sustaining proliferative signaling
The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
    ###
    INPUT: The phosphoinositide 3-kinase ( PI3K)/AKT and RAF/MEK/ERK signaling pathways are activated in a wide range of human cancers . In many cases , concomitant inhibition of both pathways is necessary to block proliferation and induce cell death and tumor shrinkage . Several feedback systems have been described in which inhibition of one intracellular pathway leads to activation of a parallel signaling pathway , thereby decreasing the effectiveness of single-agent targeted therapies . In this study , we describe a feedback mechanism in which MEK inhibition leads to activation of PI3K/AKT signaling in EGFR and HER2-driven cancers . We found that MEK inhibitor-induced activation of PI3K/AKT resulted from hyperactivation of ERBB3 as a result of the loss of an inhibitory threonine phosphorylation in the conserved juxtamembrane domains of EGFR and HER2 . Mutation of this amino acid led to increased ERBB receptor activation and upregulation of the ERBB3/PI3K/AKT signaling pathway , which was no longer responsive to MEK inhibition . Taken together , these results elucidate an important , dominant feedback network regulating central oncogenic pathways in human cancer .
    OUTPUT:
