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  • Review Article
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Molecular circuits of solid tumors: prognostic and predictive tools for bedside use

Nature Reviews Clinical Oncology volume 7, pages 367–380 (2010)Cite this article

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Abstract

The explosion of knowledge in cancer biology in the past two decades has led to the identification of specific molecular circuits in solid tumors. These pathways reflect specific abnormalities thought to drive malignant progression. This knowledge has also generated a vast panel of cancer biomarkers although many of these biomarkers lack sufficient research and validation to be used in the clinic. This Review discusses relevant molecular prognostic and/or predictive biomarkers in the six leading tumors with the highest contribution to cancer mortality: breast, lung, colorectal, prostate, pancreatic and ovarian cancer. Each biomarker is described according to its associated clinicopathological presentation and specific associated molecular interactions. Despite only few biomarkers being currently implemented in clinical practice, a new generation of predictors is emerging that could modify the classic organ-based cancer classification (for example, defects in DNA repair, aberrant MAPK signaling and aberrant PI3K/Akt/mTOR signaling). The advent of high-throughput strategies will also probably substitute monobiomarker strategies.

Key Points

  • Key oncogenic events and dysfunctional pathways have been identified over the past few decades in solid tumors

  • Many molecular-targeted agents have recently been approved or are in advanced clinical development, and these therapeutic tools target specific molecular abnormalities in the tumor allowing 'tailored treatment strategies'

  • Despite huge efforts, very few biomarkers are used in daily practice; examples of biomarkers in clinical use include ER, PR, HER2, Oncotype Dx®, MammaPrint® (breast cancer), EGFR mutations (lung cancer) and KRAS mutations (colorectal cancer)

  • Nevertheless a new generation of novel biomarkers that will modify the organ-based classification of cancer is emerging—such as DNA repair dysfunctionality, MAPK signaling and the PI3K/Akt/mTOR axis

  • Researchers and clinical investigators should be particularly aware of methodological issues when they consider biomarkers for bedside use

  • High-throughput analyses are being implemented in most tumor types, and given the huge number of possible effectors and the complex intricate pathways, high-throughput-based analysis will probably supercede monobiomarker strategies

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Figure 1: Molecular biomarkers in breast cancer.
Figure 2: Molecular biomarkers in lung cancers.
Figure 3: Molecular biomarkers in colorectal cancers.
Figure 4
Figure 5
Figure 6: Molecular biomarkers in epithelial ovarian cancers.

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Acknowledgements

The authors wish to thank C. Verjat for preparation of the figures, and C. Massard for useful comments and discussions of this manuscript.

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  1. Department of Medicine, INSERM U981, Institut Gustave Roussy, 114 rue Edouard Vaillant, 94805, Villejuif, France

    Charles Ferté, Fabrice André & Jean-Charles Soria

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  1. Charles Ferté
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  2. Fabrice André
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Correspondence to Jean-Charles Soria.

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Ferté, C., André, F. & Soria, JC. Molecular circuits of solid tumors: prognostic and predictive tools for bedside use. Nat Rev Clin Oncol 7, 367–380 (2010). https://doi.org/10.1038/nrclinonc.2010.84

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