Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Overview
  • Published:

The cancer biomarker problem

Nature volume 452, pages 548–552 (2008)Cite this article

Abstract

Genomic technologies offer the promise of a comprehensive understanding of cancer. These technologies are being used to characterize tumours at the molecular level, and several clinical successes have shown that such information can guide the design of drugs targeted to a relevant molecule. One of the main barriers to further progress is identifying the biological indicators, or biomarkers, of cancer that predict who will benefit from a particular targeted therapy.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Types of biomarker.
Figure 2: Biomarkers in the PI(3)K–PTEN–mTOR pathway.

References

  1. Hunter, D. J., Khoury, M. J. & Drazen, J. M. Letting the genome out of the bottle — will we get our wish? N. Engl. J. Med. 358, 105–107 (2008).

    Article  CAS  Google Scholar 

  2. Committee on Developing Biomarker-Based Tools for Cancer Screening, Diagnosis, and Treatment. Cancer Biomarkers: the Promises and Challenges of Improving Detection and Treatment (eds Nass, S. J. & Moses, H. L.) (National Academies Press, Washington DC, 2007).

  3. Ratain, M. J. & Glassman, R. H. Biomarkers in phase I oncology trials: signal, noise, or expensive distraction? Clin. Cancer Res. 13, 6545–6548 (2007).

    Article  CAS  Google Scholar 

  4. Carroll, K. J. Biomarkers in drug development: friend or foe? A personal reflection gained working within oncology. Pharm. Stat. 6, 253–260 (2007).

    Article  Google Scholar 

  5. Shah, N. P. et al. Sequential ABL kinase inhibitor therapy selects for compound drug-resistant BCR-ABL mutations with altered oncogenic potency. J. Clin. Invest. 117, 2562–2569 (2007).

    Article  CAS  Google Scholar 

  6. Sharma, S. V., Bell, D. W., Settleman, J. & Haber, D. A. Epidermal growth factor receptor mutations in lung cancer. Nature Rev. Cancer 7, 169–181 (2007).

    Article  CAS  Google Scholar 

  7. Pao, W. et al. KRAS mutations and primary resistance of lung adenocarcinomas to gefitinib or erlotinib. PLoS Med. 2, e17, doi:10.1371/journal.pmed.0020017 (2005).

    Article  Google Scholar 

  8. Khambata-Ford, S. et al. Expression of epiregulin and amphiregulin and K-ras mutation status predict disease control in metastatic colorectal cancer patients treated with cetuximab. J. Clin. Oncol. 25, 3230–3237 (2007).

    Article  CAS  Google Scholar 

  9. Mellinghoff, I. K. et al. Molecular determinants of the response of glioblastomas to EGFR kinase inhibitors. N. Engl. J. Med. 353, 2012–2024 (2005).

    Article  CAS  Google Scholar 

  10. Shah, N. P. et al. Potent transient inhibition of BCR–ABL by dasatinib leads to complete cytogenetic remissions in patients with chronic myeloid leukemia: implications for patient management and drug development. Blood 108, abstr. 2166 (2006).

    Google Scholar 

  11. Pao, W. et al. Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med. 2, e73, doi:10.1371/journal.pmed.0020073 (2005).

    Article  Google Scholar 

  12. Dowsett, M. et al. Prognostic value of Ki67 expression after short-term presurgical endocrine therapy for primary breast cancer. J. Natl Cancer Inst. 99, 167–170 (2007).

    Article  CAS  Google Scholar 

  13. Cloughesy, T. F. et al. Antitumor activity of rapamycin in a phase I trial for patients with recurrent PTEN-deficient glioblastoma. PLoS Med. 5, e8, doi:10.1371/journal.pmed.0050008 (2008).

    Article  Google Scholar 

  14. Neshat, M. S. et al. Enhanced sensitivity of PTEN-deficient tumors to inhibition of FRAP/mTOR. Proc. Natl Acad. Sci. USA 98, 10314–10319 (2001).

    Article  ADS  CAS  Google Scholar 

  15. Cristofanilli, M. et al. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N. Engl. J. Med. 351, 781–791 (2004).

    Article  CAS  Google Scholar 

  16. Shaffer, D. R. et al. Circulating tumor cell analysis in patients with progressive castration-resistant prostate cancer. Clin. Cancer Res. 13, 2023–2029 (2007).

    Article  CAS  Google Scholar 

  17. Nagrath, S. et al. Isolation of rare circulating tumour cells in cancer patients by microchip technology. Nature 450, 1235–1239 (2007).

    Article  ADS  CAS  Google Scholar 

  18. Potti, A. et al. Genomic signatures to guide the use of chemotherapeutics. Nature Med. 12, 1294–1300 (2006).

    Article  CAS  Google Scholar 

  19. Coombes, K. R., Wang, J. & Baggerly, K. A. Microarrays: retracing steps. Nature Med. 13, 1276–1277 (2007).

    Article  CAS  Google Scholar 

  20. Thomas, R. K. et al. Sensitive mutation detection in heterogeneous cancer specimens by massively parallel picoliter reactor sequencing. Nature Med. 12, 852–855 (2006).

    Article  ADS  CAS  Google Scholar 

  21. Thomas, R. K. et al. High-throughput oncogene mutation profiling in human cancer. Nature Genet. 39, 347–351 (2007).

    Article  CAS  Google Scholar 

  22. Rikova, K. et al. Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell 131, 1190–1203 (2007).

    Article  CAS  Google Scholar 

  23. Mehrian-Shai, R. et al. Insulin growth factor-binding protein 2 is a candidate biomarker for PTEN status and PI3K/Akt pathway activation in glioblastoma and prostate cancer. Proc. Natl Acad. Sci. USA 104, 5563–5568 (2007).

    Article  ADS  CAS  Google Scholar 

  24. Saal, L.H. et al. Poor prognosis in carcinoma is associated with a gene expression signature of aberrant PTEN tumor suppressor pathway activity. Proc. Natl Acad. Sci. USA 104, 7564–7569 (2007).

    Article  ADS  CAS  Google Scholar 

  25. Bild, A. H. et al. Oncogenic pathway signatures in human cancers as a guide to targeted therapies. Nature 439, 353–357 (2006).

    Article  ADS  CAS  Google Scholar 

  26. Diehl, F. et al. Detection and quantification of mutations in the plasma of patients with colorectal tumors. Proc. Natl Acad. Sci. USA 102, 16368–16373 (2005).

    Article  ADS  CAS  Google Scholar 

  27. Wang, X. et al. Autoantibody signatures in prostate cancer. N. Engl. J. Med. 353, 1224–1235 (2005).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

I thank S. Friend and T. Golub for many engaging debates about cancer biomarkers. I also thank the participants in the National Cancer Policy Forum–Institute of Medicine workshop on 3–5 October 2005 at the National Academy of Sciences, who shared their perspectives on the challenges of biomarker development. Work in my laboratory is supported by the Howard Hughes Medical Institute, the National Cancer Institute and the Doris Duke Charitable Foundation.

Author information

Authors and Affiliations

  1. Howard Hughes Medical Institute, Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, 10065, New York, USA

    Charles L. Sawyers

Authors
  1. Charles L. Sawyers
    View author publications

    You can also search for this author in PubMed Google Scholar

Ethics declarations

Competing interests

C.L.S. is a consultant to AVEO Pharmaceuticals, Cell Signaling Technology, Exelixis, Housey Pharmaceutical Research Laboratories, Medivation and Merck & Co.

Additional information

Reprints and permissions information is available at http://npg.nature.com/reprints.

Correspondence should be addressed to the author (sawyersc@mskcc.org).

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sawyers, C. The cancer biomarker problem. Nature 452, 548–552 (2008). https://doi.org/10.1038/nature06913

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature06913

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing