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Methodological and practical challenges for personalized cancer therapies

Nature Reviews Clinical Oncology volume 8, pages 135–141 (2011)Cite this article

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Abstract

Many experts agree that personalized cancer medicine, defined here as treatment based on the molecular characteristics of a tumor from an individual patient, has great potential in the therapy of many types of cancer. Although targeted therapy agents are increasingly available for clinical applications, many of these promising drugs have produced disappointing results when tested in clinical trials, indicating that there are many challenges that must be addressed to advance this field. We propose that a new generation of clinical trials requiring biopsies to obtain relevant tumor specimens, as well as novel statistical designs, will be essential to improve treatment outcomes. However, these novel clinical trials will only be successful if appropriate biomarkers are identified to help guide the selection of the most beneficial treatments for the participating patients. Although biomarkers based on single gene mutations are the most commonly used in clinical applications today, gene-expression or protein-expression 'signatures' and new imaging technologies have the potential to play important roles as biomarkers in the future. Therefore, it is of crucial importance that we identify and resolve existing challenges that may impede the rapid identification and translation of validated biomarkers with acceptable sensitivity and specificity from the laboratory to the clinic. These challenges include limitations of current biomarker development methodologies and regulatory and reimbursement policies and practices.

Key Points

  • Many promising targeted therapy agents have had disappointing results when tested in clinical trials

  • Validated biomarkers with acceptable sensitivity and specificity are urgently needed to help guide the selection of the most beneficial treatments for patients with cancer

  • A new generation of clinical trials requiring biopsies to obtain relevant tumor specimens, as well as novel statistical designs, will be essential to improve treatment outcomes

  • Molecular imaging of novel biomarkers or targets can add valuable spatial dimension and temporal data that could substantially improve assessments of targeted treatment efficacy

  • Current challenges include the limitations of current biomarker and imaging agent development methodologies, particularly for the molecular analysis of small tissue specimens, and regulatory and reimbursement policies

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Figure 1: Tissue availability for biomarker discovery.
Figure 2: Development of agents for biomarker imaging.

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Acknowledgements

This work was supported in part by the Department of Defense Grant W81XWH-6-1-0303 and the NIH/NCI Cancer Center Support Grant P30 CA016672. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NCI or NIH.

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Authors and Affiliations

  1. Department of Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, 77030, TX, USA

    Ignacio I. Wistuba

  2. Department of Experimental Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, 77030, TX, USA

    Juri G. Gelovani

  3. Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, 77030, TX, USA

    Jörg J. Jacoby, Suzanne E. Davis & Roy S. Herbst

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  1. Ignacio I. Wistuba
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Contributions

I. I. Wistuba, J. G. Gelovani, J. J. Jacoby and R. S. Herbst researched data to include in the manuscript. All the authors contributed to discussion of content for the article, reviewed and edited the manuscript before submission, and revised the manuscript in response to the peer-reviewers' comments.

Corresponding author

Correspondence to Roy S. Herbst.

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Competing interests

J. G. Gelovani declares he is a consultant for Macrocyclics Inc. and SibTech. He also receives grant/research support from General Electric, the NIH and the M. D. Anderson Cancer Center, and is a holder of a patent application from the M. D. Anderson Cancer Center. The other authors declare no competing interests.

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Wistuba, I., Gelovani, J., Jacoby, J. et al. Methodological and practical challenges for personalized cancer therapies. Nat Rev Clin Oncol 8, 135–141 (2011). https://doi.org/10.1038/nrclinonc.2011.2

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