Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR Cascade Inhibitors: How Mutations Can Result in Therapy Resistance and How to Overcome Resistance

@inproceedings{McCubrey2012RasRafMEKERKAP,
  title={Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR Cascade Inhibitors: How Mutations Can Result in Therapy Resistance and How to Overcome Resistance},
  author={James A McCubrey and Linda S. Steelman and William Harvey Chappell and Stephen L. Abrams and Richard A. Franklin and Giuseppe Montalto and Melchiorre Cervello and Massimo Libra and Saverio Candido and Graziella Malaponte and Maria Clorinda Mazzarino and Paolo Fagone and Ferdinando Nicoletti and Joerg Baesecke and Sanja Mijatovi{\'c} and Danijela Maksimovi{\'c}-Ivani{\'c} and Michele Milella and Agostino Tafuri and Francesca Chiarini and Camilla Evangelisti and Lucio Cocco and Alberto M Martelli},
  booktitle={Oncotarget},
  year={2012}
}
The Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR cascades are often activated by genetic alterations in upstream signaling molecules such as receptor tyrosine kinases (RTK). Targeting these pathways is often complex and can result in pathway activation depending on the presence of upstream mutations (e.g., Raf inhibitors induce Raf activation in cells with wild type (WT) RAF in the presence of mutant, activated RAS) and rapamycin can induce Akt activation. Targeting with inhibitors directed at two… CONTINUE READING

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