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Managing drug resistance in cancer: lessons from HIV therapy

Nature Reviews Cancer volume 12, pages 494–501 (2012)Cite this article

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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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  1. and the Department of Laboratory Medicine, Christoph Bock is at the CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria, Medical University of Vienna, 1090 Vienna, Austria.,

    Christoph Bock

  2. Christoph Bock and Thomas Lengauer are at the Max Planck Institute for Informatics, 66123 Saarbrücken, Germany.,

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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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