演題抄録

シンポジウム

開催概要
開催回
第51回・2013年・京都
 

がん分子標的療法に伴う代謝異常

演題番号 : S6-4

[筆頭演者]
石井 雅巳:1 

1:ノバルティスファーマ株式会社 オンコロジー事業本部 オンコロジー早期臨床開発部

 

Recent advances in cancer biology have led to development of a number of molecularly targeted agents, some of which have already been integrated into clinical practice. However, if the oncogenic pathway shares metabolic signaling, agents targeting that pathway may cause metabolic toxicities. The phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway is one of the most attractive targets for therapeutic intervention in human cancer, since many components in this pathway are frequently mutated in cancer cells. The PI3K/Akt/mTOR pathway has been found to play critical regulatory roles in diverse range of cellular processes including survival, proliferation, differentiation, migration and metabolism. Effects of the PI3K/Akt/mTOR pathway on metabolism include the promotion of glucose uptake by stimulating the membrane translocation of a glucose transporter, the activation of glycogen synthase through the inhibition of glycogen synthase kinase 3 (GSK3), the inhibition of gluconeogenesis by blocking transcription of gluconeogenic enzymes, and the regulation of fatty-acid synthesis. Clinical experiences have also shown that the inhibition of PI3K/Akt/mTOR pathways results in metabolic changes which include hyperglycemia, hypercholesteremia and hypertriglyceridemia. Among these metabolic changes, hyperglycemia is one of the most frequently observed toxicities of PI3K/Akt/mTOR inhibitors, and it is considered to be a class effect of PI3K/Akt/mTOR inhibitions. Appropriate management of such metabolic toxicities is thought to be important in order to have better treatment outcome. Attempts are also being made to utilize metabolic changes as possible biomarkers for the treatment. Metabolic changes observed with targeted therapies will be reviewed, and management and biomarker possibilities of metabolic changes will be discussed.

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