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Managing drug resistance in cancer: lessons from HIV therapy

Abstract

Drug resistance is a common cause of treatment failure for HIV infection and cancer. The high mutation rate of HIV leads to genetic heterogeneity among viral populations and provides the seed from which drug-resistant clones emerge in response to therapy. Similarly, most cancers are characterized by extensive genetic, epigenetic, transcriptional and cellular diversity, and drug-resistant cancer cells outgrow their non-resistant peers in a process of somatic evolution. Patient-specific combination of antiviral drugs has emerged as a powerful approach for treating drug-resistant HIV infection, using genotype-based predictions to identify the best matched combination therapy among several hundred possible combinations of HIV drugs. In this Opinion article, we argue that HIV therapy provides a 'blueprint' for designing and validating patient-specific combination therapies in cancer.

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Figure 1: Molecularly targeted therapy for HIV infection and cancer.
Figure 2: Towards patient-specific combination therapies for tackling drug resistance in cancer.

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Acknowledgements

The authors would like to thank K. Boztug, R. Kaiser, R. Kralovics, S. Nijman and G. Superti-Furga for helpful discussions. This work has been carried out in the context of the BLUEPRINT project (funded by the European Union (EU) under grant HEALTH-F5-2011-282510). The work of T.L. has also been supported by the CHAIN project (funded by the EU under grant HEALTH-F3-2009-223131), the HIV Cell Entry project (funded by the German Ministry of Science and Education (BMBF) under grant 0315480A) and the Oncogene project (funded by the BMBF under grant 01GS08103).

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Bock, C., Lengauer, T. Managing drug resistance in cancer: lessons from HIV therapy. Nat Rev Cancer 12, 494–501 (2012). https://doi.org/10.1038/nrc3297

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