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: PURPOSE : Prostate cancer ( PCa ) development is often associated with deletion or silencing of tumor suppressor PTEN , a negative regulator of the PI3K-Akt pathway , leading to resistance to various therapies . Therefore , the PI3K/Akt pathway plays a central role in various cellular processes leading to malignant phenotype , and , consequently is an attractive target . However , the efficacy of AKT inhibitors is limited by resistance mechanisms that result in minimal tumor cell death . Methods:Effects of Akt inhibitor AZD5363 were investigated on cell proliferation , apoptosis , Akt pathway and survival mechanisms . We then examined the impacts of inhibition of autophagy combined with AZD5363 on cell proliferation and apoptosis . Furthermore , the anti-cancer activity of combination treatment of the lysosomotropic inhibitor of autophagy ( chloroquine ) with Akt inhibitor AZD5363 was evaluated in PC-3 prostate cancer xenografts . RESULTS : we show that AZD5363 affected Akt downstream pathway by reducing p-mTOR , p-P70S6K and p-S6K . While AZD5363 monotherapy induced G2 growth arrest and autophagy , it failed to induce significant apoptosis in PC-3 and DU145 PCa cells . Blocking autophagy using pharmacological inhibitors or genetic inhibitors enhanced cell death induced by AZD5363 in these PCa cells . Importantly , the combination of AZD5363 with chloroquine significantly reduced tumor volume by 84.9% compared with the control group and by 77.5% compared with either drug alone in PC3 xenografts . CONCLUSIONS : These data demonstrate that Akt inhibitor AZD5363 , synergizes with the lysosomotropic inhibitor of autophagy , chloroquine , to induce apoptosis and delay tumor progression in PCa models that are resistant to monotherapy AZD5363 , providing a new therapeutic approach potentially translatable to patients .
    OUTPUT:

agent
sustaining proliferative signaling;resisting cell death
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: PURPOSE : Prostate cancer ( PCa ) development is often associated with deletion or silencing of tumor suppressor PTEN , a negative regulator of the PI3K-Akt pathway , leading to resistance to various therapies . Therefore , the PI3K/Akt pathway plays a central role in various cellular processes leading to malignant phenotype , and , consequently is an attractive target . However , the efficacy of AKT inhibitors is limited by resistance mechanisms that result in minimal tumor cell death . Methods:Effects of Akt inhibitor AZD5363 were investigated on cell proliferation , apoptosis , Akt pathway and survival mechanisms . We then examined the impacts of inhibition of autophagy combined with AZD5363 on cell proliferation and apoptosis . Furthermore , the anti-cancer activity of combination treatment of the lysosomotropic inhibitor of autophagy ( chloroquine ) with Akt inhibitor AZD5363 was evaluated in PC-3 prostate cancer xenografts . RESULTS : we show that AZD5363 affected Akt downstream pathway by reducing p-mTOR , p-P70S6K and p-S6K . While AZD5363 monotherapy induced G2 growth arrest and autophagy , it failed to induce significant apoptosis in PC-3 and DU145 PCa cells . Blocking autophagy using pharmacological inhibitors or genetic inhibitors enhanced cell death induced by AZD5363 in these PCa cells . Importantly , the combination of AZD5363 with chloroquine significantly reduced tumor volume by 84.9% compared with the control group and by 77.5% compared with either drug alone in PC3 xenografts . CONCLUSIONS : These data demonstrate that Akt inhibitor AZD5363 , synergizes with the lysosomotropic inhibitor of autophagy , chloroquine , to induce apoptosis and delay tumor progression in PCa models that are resistant to monotherapy AZD5363 , providing a new therapeutic approach potentially translatable to patients .
    OUTPUT:
