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Technology Insight: pharmacoproteomics for cancer—promises of patient-tailored medicine using protein microarrays

Nature Clinical Practice Oncology volume 3, pages 256–268 (2006)Cite this article

Abstract

Patient-tailored medicine can be defined as the selection of specific therapeutics to treat disease in a particular individual based on genetic, genomic or proteomic information. While individualized treatments have been used in medicine for years, advances in cancer treatment have now generated a need to more precisely define and identify those patients who will derive the most benefit from new-targeted agents. Cellular signaling pathways are a protein-based network, and the intended drug effect is to disrupt aberrant protein phosphorylation-based enzymatic activity and epigenetic phenomena. Pharmacoproteomics, or the tailoring of therapy based on proteomic knowledge, will begin to take a central role in this process. A new type of protein array platform, the reverse-phase protein microarray, shows potential for providing detailed information about the state of the cellular 'circuitry' from small samples such as patient biopsy specimens. Measurements of hundreds of specific phosphorylated proteins that span large classes of important signaling pathways can be obtained at once from only a few thousand cells. Clinical implementation of these new proteomic tools to aid the clinical, medical and surgical oncologist in making decisions about patient care will now require thoughtful communication between practicing clinicians and research scientists.

Key Points

  • An ever-increasing number of molecularly targeted agents for treating cancer are entering clinical use, generating a new need to better define and identify those patients who will most benefit from them

  • Proteomic technologies may eventually hold a dominant position in tailored medicine as we transition from pharmacogenomics to pharmacoproteomics, since gene transcript profiling cannot be used effectively to elucidate or monitor protein–protein interaction networks and signal transduction pathways

  • Protein microarrays that examine post-translational modifications, such as phosphorylation, in a global, high-throughput manner, can be used to profile the working state of cellular signaling pathways in human tissue

  • The reverse-phase protein microarray (RPA) format is uniquely suited to signal transduction profiling of small samples (e.g. biopsy specimens) such that rational selection and monitoring of patients for targeted medicine is now technically possible

  • Clinical implementation of RPAs for profiling patient tissue specimens before, during and after therapy could provide important diagnostic and prognostic information, and could help therapeutic decision making and monitoring of response or resistance

  • Establishment of RPAs or any stratification tool as routine clinical practice will require standardization of tissue collection and processing, and the cooperation and collaboration of surgeons, oncologists, pathologists and scientists

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Figure 1: A roadmap for individualized cancer therapy.
Figure 2: Reverse-phase protein microarray construction.
Figure 3: New paradigm for treating advanced-stage metastatic disease using pharmacoproteomics.
Figure 4: Tailored combination therapy offers the hope of greater efficacy with reduced toxicity.

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Author information

Authors and Affiliations

  1. Research Professor,

    Julia D Wulfkuhle, Lance A Liotta & Emanuel F Petricoin III

  2. Co-Director,

    Lance A Liotta

  3. the Co-Director, Center for Applied Proteomics Molecular Medicine, George Mason University, Manassas, VA

    Emanuel F Petricoin III

  4. Inova Fairfax Hospital Cancer Center,

    Kirsten H Edmiston

  5. Departments of Surgery, Virginia Commonwealth University, VA

    Kirsten H Edmiston

  6. Georgetown University, Washington, DC, USA

    Kirsten H Edmiston

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  1. Julia D Wulfkuhle
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  4. Emanuel F Petricoin III
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Correspondence to Julia D Wulfkuhle or Emanuel F Petricoin III.

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Wulfkuhle, J., Edmiston, K., Liotta, L. et al. Technology Insight: pharmacoproteomics for cancer—promises of patient-tailored medicine using protein microarrays. Nat Rev Clin Oncol 3, 256–268 (2006). https://doi.org/10.1038/ncponc0485

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