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.
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References
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).
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).
Ratain, M. J. & Glassman, R. H. Biomarkers in phase I oncology trials: signal, noise, or expensive distraction? Clin. Cancer Res. 13, 6545–6548 (2007).
Carroll, K. J. Biomarkers in drug development: friend or foe? A personal reflection gained working within oncology. Pharm. Stat. 6, 253–260 (2007).
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).
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).
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).
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).
Mellinghoff, I. K. et al. Molecular determinants of the response of glioblastomas to EGFR kinase inhibitors. N. Engl. J. Med. 353, 2012–2024 (2005).
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).
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).
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).
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).
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).
Cristofanilli, M. et al. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N. Engl. J. Med. 351, 781–791 (2004).
Shaffer, D. R. et al. Circulating tumor cell analysis in patients with progressive castration-resistant prostate cancer. Clin. Cancer Res. 13, 2023–2029 (2007).
Nagrath, S. et al. Isolation of rare circulating tumour cells in cancer patients by microchip technology. Nature 450, 1235–1239 (2007).
Potti, A. et al. Genomic signatures to guide the use of chemotherapeutics. Nature Med. 12, 1294–1300 (2006).
Coombes, K. R., Wang, J. & Baggerly, K. A. Microarrays: retracing steps. Nature Med. 13, 1276–1277 (2007).
Thomas, R. K. et al. Sensitive mutation detection in heterogeneous cancer specimens by massively parallel picoliter reactor sequencing. Nature Med. 12, 852–855 (2006).
Thomas, R. K. et al. High-throughput oncogene mutation profiling in human cancer. Nature Genet. 39, 347–351 (2007).
Rikova, K. et al. Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell 131, 1190–1203 (2007).
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).
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).
Bild, A. H. et al. Oncogenic pathway signatures in human cancers as a guide to targeted therapies. Nature 439, 353–357 (2006).
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).
Wang, X. et al. Autoantibody signatures in prostate cancer. N. Engl. J. Med. 353, 1224–1235 (2005).
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.
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C.L.S. is a consultant to AVEO Pharmaceuticals, Cell Signaling Technology, Exelixis, Housey Pharmaceutical Research Laboratories, Medivation and Merck & Co.
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Correspondence should be addressed to the author (sawyersc@mskcc.org).
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Sawyers, C. The cancer biomarker problem. Nature 452, 548–552 (2008). https://doi.org/10.1038/nature06913
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DOI: https://doi.org/10.1038/nature06913
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