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Genomic biomarkers in predictive medicine: an interim analysis.

Simon R - EMBO Mol Med (2011)

View Article: PubMed Central - PubMed

Affiliation: Biometric Research Branch, National Cancer Institute, Bethesda, MD, USA. rsimon@nih.gov

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Current genomics and biotechnology promise the development of biomarkers to predict individual disease risk, enable early detection of disease, and improve diagnostic classification to better inform individualized treatment... Biomarkers are biological measurements that can be used to predict risk of disease, to enable early detection of disease, to improve treatment selection and to monitor the outcome of therapeutic interventions... For example, the OncotypeDx recurrence score and MammaPrint signature are used to determine whether a woman with node-negative hormone-receptor-positive breast cancer has a sufficiently good prognosis with local treatment and adjuvant hormonal treatment that she does not require cytotoxic chemotherapy (Paik et al, ; Van de Vijver et al, )... In oncology, there is an enormous literature of claims for improved prognostic factors that have never found clinical application... The purpose of prognostic signatures like the Oncotype Dx recurrence score and the MammaPrint signature is to help patients and physicians in making informed therapeutic decisions... Useful tools like Oncotype Dx and MammaPrint should not be criticized because they do not provide biological insight into the disease. ‘Predictive biomarkers’ indicate which patients are most likely or unlikely to benefit from a specific treatment... Some of these roadblocks are discussed below and some suggested approaches for improving translational research are depicted in Fig 2... First, basic research does not go far enough in identifying the key steps in the development and pathogenesis of most chronic diseases in order to enable translational research to proceed effectively... Even in oncology, our very limited understanding of the oncogenesis of cancer is a major hurdle to effective translational research (Simon, )... Once basic research identifies a key step of oncogenesis and a druggable molecular target, the pharmaceutical and biotechnology industries are often adept at developing potent inhibitors of that target... We still do not fully understand the development and progression of any type of cancer even if, in rare cases such as CML, our knowledge of oncogenesis has been sufficient to develop effective treatments... Developing feasible pharmacologic ways of interfering with mutated p53 or Rb in tumours are difficult, long-term, high-risk endeavours that are not adequately addressed either by industry or by the culture of the NIH investigator-initiated grant system... It is not just that these problems are scientifically difficult, it is that existing mechanisms for supporting research and most existing research organizations do not provide an effective framework for a concerted effort to tackle these problems... It has not, however, elucidated the basic steps in the development and pathogenesis of many major chronic diseases nor has it provided adequate identification of key targets to enable effective translational research.

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Broad categories of intended use of biomarkers.
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fig01: Broad categories of intended use of biomarkers.

Mentions: One of the greatest problems in the development and validation of biomarkers is the ambiguity of the term and the failure to recognize that biomarker validity means fitness for intended use. An enormous amount of resources is simply wasted because researchers do not focus clearly on an intended use. This is seen, for example, in the gap between the enormous literature on prognostic biomarkers and the limited use of such markers outside research. Failure to focus also results in misleading claims for early detection biomarkers based on studies with inappropriate controls. Here, I shall discuss separately several broad categories of intended use as illustrated in Fig 1 (summarized in Box 1).


Genomic biomarkers in predictive medicine: an interim analysis.

Simon R - EMBO Mol Med (2011)

Broad categories of intended use of biomarkers.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3377087&req=5

fig01: Broad categories of intended use of biomarkers.
Mentions: One of the greatest problems in the development and validation of biomarkers is the ambiguity of the term and the failure to recognize that biomarker validity means fitness for intended use. An enormous amount of resources is simply wasted because researchers do not focus clearly on an intended use. This is seen, for example, in the gap between the enormous literature on prognostic biomarkers and the limited use of such markers outside research. Failure to focus also results in misleading claims for early detection biomarkers based on studies with inappropriate controls. Here, I shall discuss separately several broad categories of intended use as illustrated in Fig 1 (summarized in Box 1).

View Article: PubMed Central - PubMed

Affiliation: Biometric Research Branch, National Cancer Institute, Bethesda, MD, USA. rsimon@nih.gov

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

Current genomics and biotechnology promise the development of biomarkers to predict individual disease risk, enable early detection of disease, and improve diagnostic classification to better inform individualized treatment... Biomarkers are biological measurements that can be used to predict risk of disease, to enable early detection of disease, to improve treatment selection and to monitor the outcome of therapeutic interventions... For example, the OncotypeDx recurrence score and MammaPrint signature are used to determine whether a woman with node-negative hormone-receptor-positive breast cancer has a sufficiently good prognosis with local treatment and adjuvant hormonal treatment that she does not require cytotoxic chemotherapy (Paik et al, ; Van de Vijver et al, )... In oncology, there is an enormous literature of claims for improved prognostic factors that have never found clinical application... The purpose of prognostic signatures like the Oncotype Dx recurrence score and the MammaPrint signature is to help patients and physicians in making informed therapeutic decisions... Useful tools like Oncotype Dx and MammaPrint should not be criticized because they do not provide biological insight into the disease. ‘Predictive biomarkers’ indicate which patients are most likely or unlikely to benefit from a specific treatment... Some of these roadblocks are discussed below and some suggested approaches for improving translational research are depicted in Fig 2... First, basic research does not go far enough in identifying the key steps in the development and pathogenesis of most chronic diseases in order to enable translational research to proceed effectively... Even in oncology, our very limited understanding of the oncogenesis of cancer is a major hurdle to effective translational research (Simon, )... Once basic research identifies a key step of oncogenesis and a druggable molecular target, the pharmaceutical and biotechnology industries are often adept at developing potent inhibitors of that target... We still do not fully understand the development and progression of any type of cancer even if, in rare cases such as CML, our knowledge of oncogenesis has been sufficient to develop effective treatments... Developing feasible pharmacologic ways of interfering with mutated p53 or Rb in tumours are difficult, long-term, high-risk endeavours that are not adequately addressed either by industry or by the culture of the NIH investigator-initiated grant system... It is not just that these problems are scientifically difficult, it is that existing mechanisms for supporting research and most existing research organizations do not provide an effective framework for a concerted effort to tackle these problems... It has not, however, elucidated the basic steps in the development and pathogenesis of many major chronic diseases nor has it provided adequate identification of key targets to enable effective translational research.

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