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Unleashing the power of inhibitors of oncogenic kinases through BH3 mimetics

Abstract

Therapeutic targeting of tumours on the basis of molecular analysis is a new paradigm for cancer treatment but has yet to fulfil expectations. For many solid tumours, targeted therapeutics, such as inhibitors of oncogenic kinase pathways, elicit predominantly disease-stabilizing, cytostatic responses, rather than tumour regression. Combining oncogenic kinase inhibitors with direct activators of the apoptosis machinery, such as the BH3 mimetic ABT-737, may unlock potent anti-tumour potential to produce durable clinical responses with less collateral damage.

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Figure 1: Regulation of apoptosis.
Figure 2: Central role of the Mek–Erk signal transduction pathway and the Bcl-2 homology domain 3 (BH3)-only protein BIM in the efficacy of oncogenic kinase inhibitors in the presence of ABT-737.

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Acknowledgements

The authors would like to acknowledge their colleagues in the Cancer Sciences Division, Southampton, UK and The Walter and Eliza Hall Institute, Melbourne, Australia, and apologize to authors whose work has not been cited in this short article for space reasons.

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Correspondence to Mark S. Cragg or Clare L. Scott.

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DATABASES

National Cancer Institute Drug Dictionary

bortezomib

cetuximab

dasatinib

erlotinib

gefitinib

imatinib

nilotinib

PD0325901

pertuzumab

rapamycin

rituximab

sunitinib

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Cragg, M., Harris, C., Strasser, A. et al. Unleashing the power of inhibitors of oncogenic kinases through BH3 mimetics. Nat Rev Cancer 9, 321–326 (2009). https://doi.org/10.1038/nrc2615

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