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: Activating K-RAS mutations occur at a frequency of 90% in pancreatic cancer , and to date no therapies exist targeting this oncogene . K-RAS signals via downstream effector pathways such as the MAPK and the PI3K signaling pathways , and much effort has been focused on developing drugs targeting components of these pathways . To better understand the requirements for K-RAS and its downstream signaling pathways MAPK and PI3K in pancreatic tumor maintenance , we established an inducible K-RAS knock down system that allowed us to ablate K-RAS in established tumors . Knock down of K-RAS resulted in impaired tumor growth in all pancreatic xenograft models tested , demonstrating that K-RAS expression is indeed required for tumor maintenance of K-RAS mutant pancreatic tumors . We further examined signaling downstream of K-RAS , and detected a robust reduction of pERK levels upon K-RAS knock down . In contrast , no effect on pAKT levels could be observed due to almost undetectable basal expression levels . To investigate the requirement of the MAPK and the PI3K pathways on tumor maintenance , three selected pancreatic xenograft models were tested for their response to MEK or PI3K inhibition . Tumors of all three models regressed upon MEK inhibition , but showed less pronounced response to PI3K inhibition . The effect of MEK inhibition on pancreatic xenografts could be enhanced further by combined application of a PI3K inhibitor . These data provide further rationale for testing combinations of MEK and PI3K inhibitors in clinical trials comprising a patient population with pancreatic cancer harboring mutations in K-RAS .
    OUTPUT:

agent
genomic instability and mutation
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: Activating K-RAS mutations occur at a frequency of 90% in pancreatic cancer , and to date no therapies exist targeting this oncogene . K-RAS signals via downstream effector pathways such as the MAPK and the PI3K signaling pathways , and much effort has been focused on developing drugs targeting components of these pathways . To better understand the requirements for K-RAS and its downstream signaling pathways MAPK and PI3K in pancreatic tumor maintenance , we established an inducible K-RAS knock down system that allowed us to ablate K-RAS in established tumors . Knock down of K-RAS resulted in impaired tumor growth in all pancreatic xenograft models tested , demonstrating that K-RAS expression is indeed required for tumor maintenance of K-RAS mutant pancreatic tumors . We further examined signaling downstream of K-RAS , and detected a robust reduction of pERK levels upon K-RAS knock down . In contrast , no effect on pAKT levels could be observed due to almost undetectable basal expression levels . To investigate the requirement of the MAPK and the PI3K pathways on tumor maintenance , three selected pancreatic xenograft models were tested for their response to MEK or PI3K inhibition . Tumors of all three models regressed upon MEK inhibition , but showed less pronounced response to PI3K inhibition . The effect of MEK inhibition on pancreatic xenografts could be enhanced further by combined application of a PI3K inhibitor . These data provide further rationale for testing combinations of MEK and PI3K inhibitors in clinical trials comprising a patient population with pancreatic cancer harboring mutations in K-RAS .
    OUTPUT:
