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Sci. Signal., 26 March 2013
Vol. 6, Issue 268, p. ra20
[DOI: 10.1126/scisignal.2003483]


Editor's Summary

Using Addiction Against Cancer
Oncogene-addicted cancer cells depend on a particular oncogenic protein for survival and die when the oncogenic protein is inactivated. For example, lung cancers with an abnormally active form of the epidermal growth factor receptor (EGFR) and breast cancers with amplification of the gene encoding the human epidermal growth factor receptor 2 (HER2) regress when exposed to drugs called tyrosine kinase inhibitors that block the activity of these receptors. Bean et al. analyzed breast and lung cancer cell lines treated with tyrosine kinase inhibitors and mice in which EGFRs were inactivated by genetic ablation. They found that two signaling pathways, the phosphoinositide 3-kinase (PI3K)–AKT and mitogen-activated or extracellular signal–regulated protein kinase kinase (MEK)–extracellular signal–regulated kinase (ERK) pathways, were inactivated, resulting in an increase in the abundance of PUMA and BIM, two proteins that promote cell death. Furthermore, cancer cell lines resistant to tyrosine kinase inhibitors were killed by the combination of a PI3K inhibitor and a drug that inhibits antiapoptotic proteins. Thus, pharmacologically enhancing the death pathway may overcome or prevent resistance to tyrosine kinase inhibitors.

Citation: G. R. Bean, Y. T. Ganesan, Y. Dong, S. Takeda, H. Liu, P. M. Chan, Y. Huang, L. A. Chodosh, G. P. Zambetti, J. J.- D. Hsieh, E. H.- Y. Cheng, PUMA and BIM Are Required for Oncogene Inactivation–Induced Apoptosis. Sci. Signal. 6, ra20 (2013).

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The Essential Role of p53-up-regulated Modulator of Apoptosis (Puma) and Its Regulation by FoxO3a Transcription Factor in {beta}-Amyloid-induced Neuron Death.
R. Akhter, P. Sanphui, and S. C. Biswas (2014)
J. Biol. Chem. 289, 10812-10822
   Abstract »    Full Text »    PDF »
Evaluation of the BH3-only Protein Puma as a Direct Bak Activator.
H. Dai, Y.-P. Pang, M. Ramirez-Alvarado, and S. H. Kaufmann (2014)
J. Biol. Chem. 289, 89-99
   Abstract »    Full Text »    PDF »
BIM, PUMA, and the Achilles' Heel of Oncogene Addiction.
A. Roulston, W. J. Muller, and G. C. Shore (2013)
Science Signaling 6, pe12
   Abstract »    Full Text »    PDF »

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